应用shRNA下调乳腺癌细胞survivin基因表达促进细胞凋亡及逆转耐药的研究
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摘要
第一部分 survivin基因在乳腺癌细胞株MCF-7及其耐药株MCF-7／Adr的表达
目的 检测乳腺癌细胞株MCF-7及其耐药株MCF-7／Adr中survivin基因在mRNA及蛋白水平的表达，以及两种细胞的细胞周期分布。
材料与方法 常规培养乳腺癌细胞株MCF-7、MCF-7／Adr及慢性白血病细胞株K562／AO2。设计并合成survivin引物，提取细胞总RNA，以K562／AO2细胞作为阳性对照，经RT-PCR反应，以β-actin作为内对照，进行半定量分析。用免疫细胞化学SABC法检测survivin蛋白表达，经流式细胞仪分析细胞周期和增殖指数。
结果 survivin mRNA在MCF-7、MCF-7／Adr及阳性对照K562／AO2均有表达，其中MCF-7／Adr的survivin表达约为MCF-7的3.76倍，但二者survivin表达均低于阳性对照。Survivin蛋白在胞核及胞浆均有表达，但以胞核表达为主。其中MCF-7／Adr和阳性对照K562／AO2为强阳性表达，MCF-7为阳性表达。经流式细胞仪检测，MCF-7／Adr和MCF-7的G_2／M期细胞比例分别为15.25±4.96％和12.25±4.18％，增殖指数分别为58.98±12.45％和44.23±14.99％。
Objective To investigate the expressions of survivin gene in breast cancer cell line MCF-7 and its drug-resistance cell line MCF-7/Adr and to explore the distribution of cell fractions of the two cell lines in cell cycle.
Materials and Methods Human breast cancer cell line MCF-7, the drug-resistance cell line MCF-7/Adr and leukemic cell line K562/AO2 were cultured in RPMI 1640 medium containing 10% heat-inactivated calf serum. A survivin primer was designed and synthesized. Total RNA was extracted and semi-quantitative RT-PCR was performed to detect survivin mRNA expressions in MCF-7 and MCF-7/Adr cell with K562/AO2 as positive control and β-actin as internal control. Immunocytochemistry stainining (SABC) was used to determine the expression of survivin protein with K562/AO2 as positive control. Distribution of the cell fractions in different phases of cell-cycle and proliferation index were analyzed by Flow Cytometry.
目的 检测乳腺癌细胞株MCF-7及其耐药株MCF-7／Adr中survivin基因在mRNA及蛋白水平的表达，以及两种细胞的细胞周期分布。
材料与方法 常规培养乳腺癌细胞株MCF-7、MCF-7／Adr及慢性白血病细胞株K562／AO2。设计并合成survivin引物，提取细胞总RNA，以K562／AO2细胞作为阳性对照，经RT-PCR反应，以β-actin作为内对照，进行半定量分析。用免疫细胞化学SABC法检测survivin蛋白表达，经流式细胞仪分析细胞周期和增殖指数。
结果 survivin mRNA在MCF-7、MCF-7／Adr及阳性对照K562／AO2均有表达，其中MCF-7／Adr的survivin表达约为MCF-7的3.76倍，但二者survivin表达均低于阳性对照。Survivin蛋白在胞核及胞浆均有表达，但以胞核表达为主。其中MCF-7／Adr和阳性对照K562／AO2为强阳性表达，MCF-7为阳性表达。经流式细胞仪检测，MCF-7／Adr和MCF-7的G_2／M期细胞比例分别为15.25±4.96％和12.25±4.18％，增殖指数分别为58.98±12.45％和44.23±14.99％。
Objective To investigate the expressions of survivin gene in breast cancer cell line MCF-7 and its drug-resistance cell line MCF-7/Adr and to explore the distribution of cell fractions of the two cell lines in cell cycle.
Materials and Methods Human breast cancer cell line MCF-7, the drug-resistance cell line MCF-7/Adr and leukemic cell line K562/AO2 were cultured in RPMI 1640 medium containing 10% heat-inactivated calf serum. A survivin primer was designed and synthesized. Total RNA was extracted and semi-quantitative RT-PCR was performed to detect survivin mRNA expressions in MCF-7 and MCF-7/Adr cell with K562/AO2 as positive control and β-actin as internal control. Immunocytochemistry stainining (SABC) was used to determine the expression of survivin protein with K562/AO2 as positive control. Distribution of the cell fractions in different phases of cell-cycle and proliferation index were analyzed by Flow Cytometry.
引文
1．杨纯正．肿瘤耐药研究的若干问题．中华医学杂志．2001，81(24)：1475-1478
2. Green DR. Apoptotic pathways: the roads to ruin. Cell, 1998, 94(6):695-698
3. Kim R, Tanabe K, Uchida Y, et al. Current status of the molecular mechanisms of anticancer drug-induced apoptosis. The contribution of molecular-level analysis to cancer chemotherapy. Cancer Chemother Pharmacol. 2002, 50(5):343-352.
4. Reed JC. Bcl-2: prevention of apoptosis as a mechanism of drug resistance. Hematol Oncol Clin North Am, 1995, 9(2):451-473.
5. Ambrosini G, Adida C, Altieri DC. A novel anti-apoptosis gene, survivin, expressed in Cancer and Lymphoma. Nat Med, 1997, 3(8):917-921
6. Hauser HP, Bardroff M, Pyrowolakis G, et al. A giant ubiquitin-conjugating enzyme related to IAP apoptosis inhibitors. J cell Biol, 1998, 141 (6): 1415-1422.
7. Li F, Ambrosini G, Chu EY, et al. Control of apoptosis and mitotic spindle checkpoint by survivin. Nature, 1998, 396(6711):580-584.
8. Adida C, Crotty PL, Grath JM, et al. Developmentally regulated expression of the novel cancer anti-apoptosis gene survivin in human and mouse differentiation. Am J Pathol, 1998, 152(1):43-49.
9. Lu CD, Altieri DC, Tanigawa N. Expression of a novel antipoptosis gene, Survivin, correlated with tumor cell apoptosis and p53 accumulation in gastric carcinomas. Cancer Res, 1998, 58(9): 1808-1812.
10. Kawasaki H, Altieri DC, Lu CD, et al. Inhibition of apoptosis by Survivin predicts shorter survival rates in colorectal cancer. Cancer Res, 1998, 58(22):5071-5074.
11. Tanaka K, Iwamoto S, Gon G, et al. Expression of Survivin and its relationship to loss of apoptosis in breast carcinoma. Clin Cancer Res, 2000, 6(1): 127-134
12. Monzo B M, Rosell R, Felip E. A novel anti-apoptosis gene: Reexpression of Surivivin in messenger RNA as a prognosis marker in non-small cell lung cancers. J Clic Oncol, 1999, 17(7):2100-2104
13. Ito T, Shiraki K, Sugimoto K, et al. Survivin promotes cell proliferation in human hepatocellular carcinoma. Hepatology, 2000, 31(5): 1080-1085.
14. Sugahara K, Uemura A, Harasawa H, et al. Clinical relevance of survivin as a biomarker in neoplasms, especially in adult T-cell leukemias and acute leukemias. Int J Hematol. 2004, 80(1): 52-58.
15. Kobayashi K, Hatano M, Otaki M, et al. Expression of a murine homologue of the inhibitor of apoptosis protein is related to cell proliferation. Proc Natl Acad Sci USA. 1999, 96(4): 1457-1462.
16. Ambrosini G, Adida C, Sirugo G, et al. Induction of apoptosis and inhibition of cell proliferation by surviving gene targeting. J Biochem, 1998, 273 (18): 1575-1582
17. Li F, Altieri DC. Transcriptional analysis of human surviving gene expression. Biochem J, 1999, 344, 305～311
18. Li F, Altieri DC. The cancer antiapoptosis mouse survivin gene: characterization of locus and transcriptional requirements of basal and cell cycle-dependent expression. Cancer Res. 1999, 59(13): 3143-3151.
19. Oconnor DS, Grossman D, Plescia J, et al. Regulation of apoptosis at cell division by p34cdc2 phosphorylation of survivin. Proc Natl Acad Sci USA, 2000, 97(24): 13103～13107.
20. Suzuki A, Ito T, Kawano H, et al. Survivin initiates procaspase3/p21 complex formation as a result of interaction with CDk4 to resist Fas-mediated cell death. Oncogene, 2000, 19(10): 1346-1353
21. Tamm I, Wang Y, Sausville E, et al. IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs. Cancer Res, 1998, 58(23): 5315-5320.
22. Shin S, Sung BJ, Cho YS, et al. An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and -7. Biochemistry, 2001, 40(4): 1117-1123.
23. Skoufias DA, Mollinari C, Lacroix FB, et al. Human survivin is a kinetochore-associated passenger protein. J Cell Biol, 2000, 151(7): 1575-1582.
24. Kallio MJ, Nieminen M, Eriksson JE. Human inhibitor of apoptosis protein (IAP) survivin participates in regulation of chromosome segregation and mitotic exit. FASEB J. 2001, 15(14): 2721-2723.
25. Nakamura M, Tsuji N, Asanuma K, et al. Survivin as a predictor of cis-diamminedichloroplatinum sensitivity in gastric cancer patients. Cancer Sci, 2004, 95(1): 44-51.
26. Notarbartolo M, Cervello M, Poma P, et al. Expression of the IAPs in multidrug resistant tumor cells. Oncol Rep, 2004, 11 (1): 133-136.
27. Zaffaroni N, Daidone MG. Survivin expression and resistance to anticancer treatments: perspectives for new therapeutic interventions. Drug Resist Updat, 2002, 5(2): 65-72.
28. Wang L, Zhang GM, Feng ZH. Down-regulation of survivin expression reversed multidrug resistance in adriamycin-resistant HL-60/ADR cell line. Acta Pharmacol Sin, 2003, 24(12): 1235-1240.
29. Olie RA, Simoes-Wust AP, Baumann B, et al. A novel antisense oligonucleotide targeting survivin expression induces apoptosis and sensitizes lung cancer cells to chemotherapy. Cancer Res, 2000, 60(11): 2805-2809.
30. Fire A, Xu S, Montgomery MK, et al. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature, 1998, 391 (6669): 806-811.
31. Elbashir SM, Harborth J, Lendeckel W, et al. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature, 2001, 411 (6836): 494-498.
32. Couzin J. Break through of the year: Small RNAs make big splash[J]. Science, 2002, 298(5602): 2296-2297.
33. Dykxhoorn DM, Novina CD, Sharp PA. Killing the messenger: short RNAs that silence gene expression. Nat Rev Mol Cell Biol. 2003, 4(6): 457-467.
34. Meister G, Tuschl T. Mechanisms of gene silencing by double-stranded RNA. Nature, 2004, 431(7006): 343-349.
35. Tijsterman M, Plasterk RH. Dicers at RISC; the mechanism of RNAi. Cell. 2004, 117(1): 1-3.
36. Wilda M, Fuchs U, Wossmann W, et al. Killing of leukemic cells with a BCR/ABL fusion gene by RNA interference (RNAi). Onco gene, 2002, 21(37): 5716-5724.
37. Yang G, Thompson JA, Fang B, et al. Silencing of H-ras gene expression by retrovirus- mediated siRNA decreases transformation efficiency and tumor growth in a model of human ovarian cancer. Oncogene, 2003, 22(36): 5694-5701.
38. Tarnawski A, Pai R, Chiou SK, et al. Rebamipide inhibits gastric cancer growth by targeting survivin and Aurora-B. Biochem Biophys Res Commun, 2005, 334(1): 207-212.
1．薛军，林茂芳，蔡真．血液肿瘤细胞株细胞survivin基因表达以及ATRA对NB4细胞株survivin基因表达的调节。中国病理生理杂志，2004，20(2)：234-237
2. Ambrosini G, Adida C, Altieri DC. A novel anti-apoptosis gene, survivin, expressed in Cancer and Lymphoma. Nature Med, 1997, 3(8):917～921
3. Iamm I, Wang Y, Sausville ED, et al. Cancer Res, 1998, 58(11):5315-5320
4. Li F, Altieri DC. Transcriptional analysis of human survivin gene expression. Biochem J. 1999, 344 Pt 2:305-311.
5. Kallio MJ, Nieminen M, Eriksson JE, et al. Human inhibitor of apoptosis protein survivin participates in regulation of chromosome segregation and mitotic exit. FASEB J, 2001, 15(14):2721-2723
6. Satoh K, Kaneko K, Hirota M, et al. Expression of survivin is correlated with cancer cell apoptosis and is involved in the development of human pancreatic duct cell tumors. Cancer, 2001, 92(2):271-278.
7. Tanaka K, I wamoto S, Gon G. et al. Expression of Survivin and its relationship to loss of apoptosis in breast carcinoma. Clin Cancer Res, 2000, 6(1): 127-134.
8. Nasu S, Yagihashi A, Izawa A, et al. Survivin Mrna expression in patients with breast cancer. Anticancer Res, 2002, 22(3):1839-1843
9. Olie RA, Simoes-Wust AP, Baumann B, et al. A novel antisense oligonucleotide targeting survivin expression induces apoptosis and sensitizes lung cancer cells to chemotherapy. Cancer Res, 2000, 60(11):2805-2809
10. Kawasaki H, Altieri DC, Lu CD, et al. Inhibition of apoptosis by Survivin predicts shorter survival rates in colorectal cancer. Cancer Res, 1998, 58(22):5071-5074.
11. Suzuki A, Ito T, Kawano H, et al. Survivin initiates procaspase3/p21 complex formation as a result of interaction with CDk4 to resist Fas-mediated cell death. Oncogene, 2000, 19(10): 1346-1353
12. Nakamura M, Tsuji N, Asanuma K, et al. Survivin as a predictor of cis-diamminedichloroplatinum sensitivity in gastric cancer patients. Cancer Sci, 2004, 95(1): 44-51.
13. Lu CD, Altieri DC, Tanigawa N, et al. Expression of a novel antipoptosis gene, Survivin, correlated with tumor cell apoptosis and p53 accumulation in gastric carcinomas. Cancer Res, 1998, 58(9): 1808-1812.
14. Okada E, Murai Y, Mstsui K, et al. Survivin expression in tumor cell nuclei is predictive of a favorable prognosis in gastric cancer patients. Cancer lett, 2001, 163(1): 109-116
15. Rodriguez JA, Span SW, Ferreira CG, et al. CRM1-mediated nuclear export determines the cytoplasmic localization of the antiapoptotic protein Survivin. Exp Cell Res, 2002, 275(1): 44-53
16. Fortugno P, Wall NR, Giodini A, et al. Surviivin exists in immuno-chemically distinct subcellular pools and is involved in spindle microtuble function. J Cell Sci, 2002, 115(4): 575-585
17. Li F, Ambrosini G, Chu EY, et al. Control of apoptosis and mitotic spindle checkpoint by survivin. Nature, 1998, 396(6711): 580-584.
1. Dykxhoorn DM, Novina CD, Sharp PA. Killing the messenger: short RNAs that silence gene expression. Nat Rev Mol Cell Biol, 2003, 4(6): 457-467.
2. Fire A, Xu S, Montgomery MK, et al. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature, 1998, 391(6669): 806-811.
3. Elbashir SM, Harborth J, Lendeckel W, et al. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature, 2001, 411(6836): 494-498.
4. Caplen NJ, Parrish S, Imani F, et al. Specific inhibition of gene expression by small double-stranded RNAs in invertebrate and vertebrate systems. Proc Natl Acad Sci U S A, 2001, 98(17): 9742-9747.
5. Brummelkamp TR, Bernards R, Agami R. A system for stable expression of short interfering RNAs in mammalian cells. Science, 2002, 296(5567): 550-553.
6. Lee NS, Dohjima T, Bauer G, et al. Expression of small interfering RNAs targeted against HIV-1 rev transcripts in human cells. Nat Biotechnol, 2002, 20(5): 500-505.
7. Yu JY, De Ruiter SL, Turner DL. RNA interference by expression of short-interfering RNAs and hairpin RNAs in mammalian cells. Proc Natl Acad Sci U S A. 2002, 99(9): 6047-6052.
8. Harmon GJ. RNA interference. Nature, 2002, 418(6894): 244-251.
9. Paddison PJ, Caudy AA, Hannon GJ. Stable suppression of gene expression by RNAi in mammalian cells. Proc Natl Acad Sci U S A, 2002, 99(3): 1443-1448.
10. Miyagishi M, Taira K. U6 promoter-driven siRNAs with four uridine 3' overhangs efficiently suppress targeted gene expression in mammalian cells. Nat Biotechnol, 2002, 20(5): 497-500.
11. Tuschl T, Zamore PD, Lehmann R, et al. Targeted mRNA degradation by double-stranded RNA in vitro. Genes Dev, 1999, 13(24): 3191-3197.
12. Elbashir SM, Lendeckel W, Tuschl1 T, et al. RNA interference is mediated by 21- and 22-nucleotide RNAs. Genes Dev, 2001, 15(2): 188-200.
13. Zhang L, Yang N, Mohamed-Hadley A, et al. Vector-based RNAi, a novel tool for isoform-specific knock-down of VEGF and anti-angiogenesis gene therapy of cancer. Biochem Biophys Res Commun, 2003, 303(4): 1169-1178.
14. Li K, Lin SY, Brunicardi FC, et al. Use of RNA interference to target cyclin E-overexpressing hepatocellular carcinoma. Cancer Res, 2003, 63(13):3593-3597.
15. Chen Y, Du D, Wu J, et al. Inhibition of hepatitis B virus replication by stably expressed shRNA. Biochem Biophys Res Commun, 2003, 311(2):398-404.
16. Kretschmer-Kazemi Far R, Sczakiel G. The activity of siRNA in mammalian cells is related to structural target accessibility: a comparison with antisense oligonucleotides. Nucleic Acids Res. 2003, 31 (15):4417-4424.
17. Bohula EA, Salisbury AJ, Sohail M, et al. The efficacy of small interfering RNAs targeted to the type 1 insulin-like growth factor receptor (IGF1R) is influenced by secondary structure in the IGF1R transcript. J Bio Chem, 2003, 278(18): 15991～15997
18. Lee NS, Dohjima T, Bauer G, et al. Expression of small interfering RNAs targeted against HIV-1 rev transcriptis in human cells. Nat Biotech, 2002, 20(5):500～505
19. Vickers TA, Koo S, Bennett CF et al. Efficient reduction of target RNAs by small interfering RNA and Rnase H2 dependent antisense agents. J Biol Chem, 2003, 278(9):7108～7118
20．夏云，林汝仙，郑素军等．靶向端粒酶逆转录酶(hTERT)RNAi载体的构建及活性评价．生物化学与生物物理进展．2004，31(12)：1079-1084
1. Bontenbal M, Nortier JW, Beex LV, et al. Adjuvant systemic therapy for patients with respectable breast cancer: guideline from the Dutch National Breast Cancer Plat form and the Dutch Society for Medical. Oncology Ned Tijdschr Geneeskd, 2000, 144(21):984-989.
2. Hussain SA, Palmer DH, Stevens A, et al. Role of chemotherapy in breast cancer. Expert Rev Anticancer Ther, 2005, 5(6): 1095-1110.
3. O'Shaughnessy J. Extending survival with chemotherapy in metastatic breast cancer. Oncologist, 2005; 10 Suppl 3:20-29.
4. Hait WN, Yang JM. Clinical management of recurrent breast cancer: development of multidrug resistance (MDR) and strategies to circumvent it. Semin Oncol, 2005, 32(6 Suppl 7):S16-21.
5. Lehnert M. Chemotherapy resistance in breast cancer. Anticancer Res, 1998, 18(3 C):2225-2226
6. Sun YL, Zhou GY, Li KN, Suppression of glucosylceramide synthase by RNA interference reverses multidrug resistance in human breast cancer cells. Neoplasma, 2006; 53(1):1-8.
7. Lopes de Menezes DE, Hu Y, Mayer LD. Combined treatment of Bcl-2 antisense oligodeoxynucleotides (G3139), p-glycoprotein inhibitor (PSC833), and sterically stabilized liposomal doxorubicin suppresses growth of drug-resistant growth of drug-resistant breast cancer in severely combined immunodeficient mice. J Exp Ther Oncol, 2003, 3(2):72-82.
8．吴二喜，印大中，王凤飞．核糖核酸干扰(RNAi)在生物医学研究中的应用．生命科学研究．2005，9(2)：95-98
9. Vickers TA, Koo S, Bennett CF et al. Efficient reduction of target RNAs by small interfering RNA and Rnase H2 dependent antisense agents. J Biol Chem, 2003, 278(9):7108～7118
10．夏云，林汝仙，郑素军等．靶向端粒酶逆转录酶(hTERT)RNAi载体的构建及活性评价．生物化学与生物物理进展．2004，31(12)：1079-1084
11. Zhang L, Yang N, Mohamed-Hadley A, et al. Vector-based RNAi, a novel tool for isoform-specific knock-down of VEGF and anti-angiogenesis gene therapy of cancer. Biochem Biophys Res Commun, 2003, 303(4): 1169-1178.
12. Tuschl T, Zamore PD, Lehmann R, et al. Targeted mRNA degradation by double-stranded RNA in vitro. Genes Dev, 1999, 13(24): 3191-3197.
13. Elbashir SM, Lendeckel W, Tuschl1 T, et al. RNA interference is mediated by 21-and 22-nucleotide RNAs. Genes Dev, 2001, 15(2): 188-200.
14. Miyagishi M, Taira K. U6 promoter-driven siRNAs with four uridine 3' overhangs efficiently suppress targeted gene expression in mammalian cells. Nat Biotechnol.2002, 20(5): 497-500.
15. Yu JY, De Ruiter SL, Turner DL. RNA interference by expression of short-interfering RNAs and hairpin RNAs in mammalian cells. Proc Natl Acad Sci U S A, 2002, 99(9): 6047-6052.
16. Scherr M, Morgan MA, Eder M. Gene silencing mediated by small interfering RNAs in mammalian cells. Curr Med Chem, 2003, 10(3): 245-256.
17. Lu SY, Sui YF, Li ZS, et al. Construction of a regulable gene therapy vector targeting for hepatocellular carcinoma. World J Gastroenterol, 2003, 9(4): 688-91.
18. O'Connell M J, Cimprich KA. G_2 damage checkpoints: what is the turn-on? J Cell Sci, 2005, 118(Pt 1): 1-6.
19. Zhou BB, Elledge SJ. The DNA damage response: putting checkpoints in perspective. Nature, 2000, 408(6811): 433-439.
20. Norbury CJ, Zhivotovsky B. DNA damage-induced apoptosis. Oncogene, 2004, 23(16): 2797-2808.
21. Dasika GK, Lin SC, Zhao S, et al. DNA damage-induced cell cycle checkpoints and DNA strand break repair in development and tumorigenesis. Oncogene, 1999, 18(55): 7883-7899.
22. Suzuki A, Ito T, Kawano H, et al. Survivin initiates procaspase 3/p21 complex formation as a result of interaction with Cdk4 to resist Fas-mediated cell death. Oncogene. 2000, 19(10): 1346-1353.
23. Shin S, Sung BJ, Cho YS, et al. An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and -7. Biochemistry, 2001, 40(4): 1117-1123.
24. Sugahara K, Uemura A, Harasawa H, et al. Clinical relevance of survivin as a biomarker in neoplasms, especially in adult T-cell leukemias and acute leukemias. Int J Hematol, 2004, 80(1): 52-58.
25. Kobayashi K, Hatano M, Otaki M, et al. Expression of a murine homologue of the inhibitor of apoptosis protein is related to cell proliferation. Proc Natl Acad Sci USA, 1999, 96(4): 1457-1462.
26. Fulda S, Debatin KM. Targeting apoptosis pathways in cancer therapy. Curr Cancer Drug Targets, 2004, 4(7): 569-576.
27. Stavrovskaya AA. Cellular mechanisms of multidrug resistance of tumor cells. Biochemistry (Mosc), 2000, 65(1): 95-106.
28. Reed JC. Apoptosis mechanisms: implications for cancer drug discovery. Oncology (Williston Park), 2004, 18(13 Suppl 10): 11-20.
29. Tamm I, Wang Y, Sausville E, et al. IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs. Cancer Res, 1998, 58(23): 5315-5320.
30. Nomura T, Yamasaki M, Nomura Y, et al. Expression of the inhibitors of apoptosis proteins in cisplatin-resistant prostate cancer cells. Oncol Rep, 2005, 14(4): 993-997
31. Notarbartolo M, Lo Cicero S, Meli M, et al. Induction of apoptosis by the adenosine derivative IB-MECA in parental or multidrug-resistant HL-60 leukemia cells: possible relationship to the effects on inhibitor of apoptosis protein levels. Chemotherapy, 2005, 51(5): 272-279.
32. Tarnawski A, Pai R, Chiou SK, et al. Rebamipide inhibits gastric cancer growth by targeting survivin and Aurora-B. Biochem Biophys Res Commun, 2005, 334(1): 207-212.
33. Zhang M, Mukherjee N, Bermudez RS, et al. Adenovirus-mediated inhibition of survivin expression sensitizes human prostate cancer cells to paclitaxel in vitro and in vivo. Prostate, 2005, 64(3): 293-302.
1. Anderson W F, Blaese R M, Culver K, et al. The ADA human gene therapy clinical protocol: points to consider response with clinical protocol. Hum Gene Ther, 1990, 1(3): 331～362
2. Edelstein ML, Abedi MR, Wixon J, et al. Gene therapy clinical trials worldwide 1989-2004-an overview. J Gene Med, 2004, 6(6): 597-602
3. Gura T. Hemophilia: after a setback, gene therapy progresses...gingerly. Science, 2001, 291 (5509): 1692～1697
4. Kohn D B, Sadelain M, Glorioso J C, et al. Occurrence of leukaemia following gene therapy of X-linked SCID. Nat Rev Cancer, 2003, 3(7):477～488
5. Marshall E. Gene therapy. Second child in French trial is found to have leukemia. Science, 2003, 299(5605): 320
6. Sadelain M. Insertional oncogenesis in gene therapy: how much of a risk? Gene Ther, 2004, 11(7): 569～573
7. Caplen N J, Parrish S, Imani F, et al. Proc Natl Acad Sci USA, 2001; 98: 9746～9747
8. Elbashir S M, Harborth J, Lendeckel W, et al. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature, 2001, 411 (6836): 494-498.
9. Martiniello-Wilks R, Dane A, Voeks DJ, et al. Gene-directed enzyme prodrug therapy for prostate cancer in a mouse model that imitates the development of human disease. J Gene Med, 2004, 6(1): 43-54.
10. Moon C, Oh Y, Roth JA. Current status of gene therapy for lung cancer and head and neck cancer. Clin Cancer Res, 2003, 9(14): 5055-67.
11. Sotomayor MG, Yu H, Antonia S, et al. Advances in gene therapy for malignant melanoma. Cancer Control, 2002, 9(1): 39-48.
12. Roth JA, Grammer SF, Swisher SG, et al. Gene therapy approaches for the management of non-small cell lung cancer. Semin Oncol, 2001, 28(4 Suppl 14): 50-56.
13. Asklund T, Appelskog IB, Ammerpohl O, et al. Gap junction-mediated bystander effect in primary cultures of human malignant gliomas with recombinant expression of the HSVtk gene. Exp Cell Res, 2003, 284(2): 185-195
14. Neijssen J, Herberts C, Drijfhout JW, et al. Cross-presentation by intercellular peptide transfer through gap junctions. Nature, 2005, 434(7029): 83-88.
15. Sanson M, Marcaud V, Robin E, et al. Connexin 43-mediated bystander effect in two rat glioma cell models. Cancer Gene Ther, 2002, 9(2): 149-155.
16. Howarth M, Elliott T. The processing of antigens delivered as DNA vaccines. Immunol Rev, 2004, 199: 27-39.
17. Carroll JL, Nielsen LL, Pruett SB, et al. The role of natural killer cells in adenovirus-mediated p53 gene therapy. Mol Cancer Ther, 2001, 1(1): 49-60.
18. Ray G, Banerjee S, Saxena NK, Stimulation of MCF-7 tumor progression in athymic nude mice by 17beta-estradiol induces WISP-2/CCN5 expression in xenografts: a novel signaling molecule in hormonal carcinogenesis. Oncol Rep, 2005, 13(3): 445-448.
19. Stephen R. D. Johnstonl, Irene M. Idoxifene antagonizes estradiol-dependent MCF-7 breast cancer xenograft growth through sustained induction of apoptosis. Cancer Res, 1999, 59(15): 3646-3651.
20. Motomura S, Motoji T, Takanashi M, et al. Inhibition of P-glycoprotein and recovery of drug sensitivity of human acute leukemic blast cells by multidrug resistance gene (mdr1) antisense oligonucleotides. Blood, 1998, 91(9): 3163-3171
21. Ren Y, Wei D, Zhan X. Inhibition of P-glycoprotein and increasing of drug-sensitivity of a human carcinoma cell line (KB-A-1) by an antisense oligodeoxynucleotide-doxorubicin conjugate in vitro. Biotechnol Appl Biochem, 2005, 41 (Pt 2): 137-143.
22. Ramachandran C, Wellham. Effect of MDR1 phosphorothioate antisense oligodeoxynucleotides in multidrug-resistant human tumor cell lines and xenografts. Anticancer Res, 2003, 23(3B): 2681-2690
23. Huesker M, Folmer Y, Schneider M, et al. Reversal of drug resistance of hepatocellular carcinoma cells by adenoviral delivery of anti-MDR1 ribozymes. Hepatology, 2002, 36(4 Pt 1): 874-884.
24. Nagata J, Kijima H, Hatanaka H, et al. Reversal of drug resistance using hammerhead ribozymes against multidrug resistance-associated protein and multidrug resistance 1 gene. Int J Oncol, 2002, 21(5):1021-1026.
25. Hua J, Mutch DG, Herzog TJ. Stable suppression of MDR-1 gene using siRNA expression vector to reverse drug resistance in a human uterine sarcoma cell line. Gynecol Oncol, 2005, 98(1):31-38.
26. Nieth C, Priebsch A, Stege A, et al. Modulation of the classical multidrug resistance (MDR) phenotype by RNA interference (RNAi). FEBS Lett, 2003, 545(2-3):144-150.
27. Kaufmann SH, Vaux DL. Alterations in the apoptotic machinery and their potential role in anticancer drug resistance. Oncogene, 2003, 22(47):7414-7430.
28. Davis JM, Navolanic PM, Weinstein-Oppenheimer CR, et al. Raf-1 and Bcl-2 induce distinct and common pathways that contribute to breast cancer drug resistance. Clin Cancer Res, 2003, 9(3): 1161-1170.
29. Williams J, Lucas PC, Griffith KA, et al. Expression of Bcl-xL in ovarian carcinoma is associated with chemoresistance and recurrent disease. Gynecol Oncol, 2005, 96(2):287-295.
30. Dai Y, Rahmani M, Corey SJ, et al. A Bcr/Abl-independent, Lyn-dependent form of imatinib mesylate (STI-571) resistance is associated with altered expression of Bcl-2. J Biol Chem, 2004, 279(33):34227-34239.
31．邓凯贤，钟玲，姜梅贤等．RNA干扰技术沉默survivin基因逆转卵巢癌细胞株SKOV3／ADM耐药性的研．中华妇产科杂志，2005，40(12)836-839
32. Zaffaroni N, Pennati M, Daidone MG. Survivin as a target for new anticancer interventions. J Cell Mol Med, 2005, 9(2):360-372.
2. Green DR. Apoptotic pathways: the roads to ruin. Cell, 1998, 94(6):695-698
3. Kim R, Tanabe K, Uchida Y, et al. Current status of the molecular mechanisms of anticancer drug-induced apoptosis. The contribution of molecular-level analysis to cancer chemotherapy. Cancer Chemother Pharmacol. 2002, 50(5):343-352.
4. Reed JC. Bcl-2: prevention of apoptosis as a mechanism of drug resistance. Hematol Oncol Clin North Am, 1995, 9(2):451-473.
5. Ambrosini G, Adida C, Altieri DC. A novel anti-apoptosis gene, survivin, expressed in Cancer and Lymphoma. Nat Med, 1997, 3(8):917-921
6. Hauser HP, Bardroff M, Pyrowolakis G, et al. A giant ubiquitin-conjugating enzyme related to IAP apoptosis inhibitors. J cell Biol, 1998, 141 (6): 1415-1422.
7. Li F, Ambrosini G, Chu EY, et al. Control of apoptosis and mitotic spindle checkpoint by survivin. Nature, 1998, 396(6711):580-584.
8. Adida C, Crotty PL, Grath JM, et al. Developmentally regulated expression of the novel cancer anti-apoptosis gene survivin in human and mouse differentiation. Am J Pathol, 1998, 152(1):43-49.
9. Lu CD, Altieri DC, Tanigawa N. Expression of a novel antipoptosis gene, Survivin, correlated with tumor cell apoptosis and p53 accumulation in gastric carcinomas. Cancer Res, 1998, 58(9): 1808-1812.
10. Kawasaki H, Altieri DC, Lu CD, et al. Inhibition of apoptosis by Survivin predicts shorter survival rates in colorectal cancer. Cancer Res, 1998, 58(22):5071-5074.
11. Tanaka K, Iwamoto S, Gon G, et al. Expression of Survivin and its relationship to loss of apoptosis in breast carcinoma. Clin Cancer Res, 2000, 6(1): 127-134
12. Monzo B M, Rosell R, Felip E. A novel anti-apoptosis gene: Reexpression of Surivivin in messenger RNA as a prognosis marker in non-small cell lung cancers. J Clic Oncol, 1999, 17(7):2100-2104
13. Ito T, Shiraki K, Sugimoto K, et al. Survivin promotes cell proliferation in human hepatocellular carcinoma. Hepatology, 2000, 31(5): 1080-1085.
14. Sugahara K, Uemura A, Harasawa H, et al. Clinical relevance of survivin as a biomarker in neoplasms, especially in adult T-cell leukemias and acute leukemias. Int J Hematol. 2004, 80(1): 52-58.
15. Kobayashi K, Hatano M, Otaki M, et al. Expression of a murine homologue of the inhibitor of apoptosis protein is related to cell proliferation. Proc Natl Acad Sci USA. 1999, 96(4): 1457-1462.
16. Ambrosini G, Adida C, Sirugo G, et al. Induction of apoptosis and inhibition of cell proliferation by surviving gene targeting. J Biochem, 1998, 273 (18): 1575-1582
17. Li F, Altieri DC. Transcriptional analysis of human surviving gene expression. Biochem J, 1999, 344, 305～311
18. Li F, Altieri DC. The cancer antiapoptosis mouse survivin gene: characterization of locus and transcriptional requirements of basal and cell cycle-dependent expression. Cancer Res. 1999, 59(13): 3143-3151.
19. Oconnor DS, Grossman D, Plescia J, et al. Regulation of apoptosis at cell division by p34cdc2 phosphorylation of survivin. Proc Natl Acad Sci USA, 2000, 97(24): 13103～13107.
20. Suzuki A, Ito T, Kawano H, et al. Survivin initiates procaspase3/p21 complex formation as a result of interaction with CDk4 to resist Fas-mediated cell death. Oncogene, 2000, 19(10): 1346-1353
21. Tamm I, Wang Y, Sausville E, et al. IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs. Cancer Res, 1998, 58(23): 5315-5320.
22. Shin S, Sung BJ, Cho YS, et al. An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and -7. Biochemistry, 2001, 40(4): 1117-1123.
23. Skoufias DA, Mollinari C, Lacroix FB, et al. Human survivin is a kinetochore-associated passenger protein. J Cell Biol, 2000, 151(7): 1575-1582.
24. Kallio MJ, Nieminen M, Eriksson JE. Human inhibitor of apoptosis protein (IAP) survivin participates in regulation of chromosome segregation and mitotic exit. FASEB J. 2001, 15(14): 2721-2723.
25. Nakamura M, Tsuji N, Asanuma K, et al. Survivin as a predictor of cis-diamminedichloroplatinum sensitivity in gastric cancer patients. Cancer Sci, 2004, 95(1): 44-51.
26. Notarbartolo M, Cervello M, Poma P, et al. Expression of the IAPs in multidrug resistant tumor cells. Oncol Rep, 2004, 11 (1): 133-136.
27. Zaffaroni N, Daidone MG. Survivin expression and resistance to anticancer treatments: perspectives for new therapeutic interventions. Drug Resist Updat, 2002, 5(2): 65-72.
28. Wang L, Zhang GM, Feng ZH. Down-regulation of survivin expression reversed multidrug resistance in adriamycin-resistant HL-60/ADR cell line. Acta Pharmacol Sin, 2003, 24(12): 1235-1240.
29. Olie RA, Simoes-Wust AP, Baumann B, et al. A novel antisense oligonucleotide targeting survivin expression induces apoptosis and sensitizes lung cancer cells to chemotherapy. Cancer Res, 2000, 60(11): 2805-2809.
30. Fire A, Xu S, Montgomery MK, et al. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature, 1998, 391 (6669): 806-811.
31. Elbashir SM, Harborth J, Lendeckel W, et al. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature, 2001, 411 (6836): 494-498.
32. Couzin J. Break through of the year: Small RNAs make big splash[J]. Science, 2002, 298(5602): 2296-2297.
33. Dykxhoorn DM, Novina CD, Sharp PA. Killing the messenger: short RNAs that silence gene expression. Nat Rev Mol Cell Biol. 2003, 4(6): 457-467.
34. Meister G, Tuschl T. Mechanisms of gene silencing by double-stranded RNA. Nature, 2004, 431(7006): 343-349.
35. Tijsterman M, Plasterk RH. Dicers at RISC; the mechanism of RNAi. Cell. 2004, 117(1): 1-3.
36. Wilda M, Fuchs U, Wossmann W, et al. Killing of leukemic cells with a BCR/ABL fusion gene by RNA interference (RNAi). Onco gene, 2002, 21(37): 5716-5724.
37. Yang G, Thompson JA, Fang B, et al. Silencing of H-ras gene expression by retrovirus- mediated siRNA decreases transformation efficiency and tumor growth in a model of human ovarian cancer. Oncogene, 2003, 22(36): 5694-5701.
38. Tarnawski A, Pai R, Chiou SK, et al. Rebamipide inhibits gastric cancer growth by targeting survivin and Aurora-B. Biochem Biophys Res Commun, 2005, 334(1): 207-212.
1．薛军，林茂芳，蔡真．血液肿瘤细胞株细胞survivin基因表达以及ATRA对NB4细胞株survivin基因表达的调节。中国病理生理杂志，2004，20(2)：234-237
2. Ambrosini G, Adida C, Altieri DC. A novel anti-apoptosis gene, survivin, expressed in Cancer and Lymphoma. Nature Med, 1997, 3(8):917～921
3. Iamm I, Wang Y, Sausville ED, et al. Cancer Res, 1998, 58(11):5315-5320
4. Li F, Altieri DC. Transcriptional analysis of human survivin gene expression. Biochem J. 1999, 344 Pt 2:305-311.
5. Kallio MJ, Nieminen M, Eriksson JE, et al. Human inhibitor of apoptosis protein survivin participates in regulation of chromosome segregation and mitotic exit. FASEB J, 2001, 15(14):2721-2723
6. Satoh K, Kaneko K, Hirota M, et al. Expression of survivin is correlated with cancer cell apoptosis and is involved in the development of human pancreatic duct cell tumors. Cancer, 2001, 92(2):271-278.
7. Tanaka K, I wamoto S, Gon G. et al. Expression of Survivin and its relationship to loss of apoptosis in breast carcinoma. Clin Cancer Res, 2000, 6(1): 127-134.
8. Nasu S, Yagihashi A, Izawa A, et al. Survivin Mrna expression in patients with breast cancer. Anticancer Res, 2002, 22(3):1839-1843
9. Olie RA, Simoes-Wust AP, Baumann B, et al. A novel antisense oligonucleotide targeting survivin expression induces apoptosis and sensitizes lung cancer cells to chemotherapy. Cancer Res, 2000, 60(11):2805-2809
10. Kawasaki H, Altieri DC, Lu CD, et al. Inhibition of apoptosis by Survivin predicts shorter survival rates in colorectal cancer. Cancer Res, 1998, 58(22):5071-5074.
11. Suzuki A, Ito T, Kawano H, et al. Survivin initiates procaspase3/p21 complex formation as a result of interaction with CDk4 to resist Fas-mediated cell death. Oncogene, 2000, 19(10): 1346-1353
12. Nakamura M, Tsuji N, Asanuma K, et al. Survivin as a predictor of cis-diamminedichloroplatinum sensitivity in gastric cancer patients. Cancer Sci, 2004, 95(1): 44-51.
13. Lu CD, Altieri DC, Tanigawa N, et al. Expression of a novel antipoptosis gene, Survivin, correlated with tumor cell apoptosis and p53 accumulation in gastric carcinomas. Cancer Res, 1998, 58(9): 1808-1812.
14. Okada E, Murai Y, Mstsui K, et al. Survivin expression in tumor cell nuclei is predictive of a favorable prognosis in gastric cancer patients. Cancer lett, 2001, 163(1): 109-116
15. Rodriguez JA, Span SW, Ferreira CG, et al. CRM1-mediated nuclear export determines the cytoplasmic localization of the antiapoptotic protein Survivin. Exp Cell Res, 2002, 275(1): 44-53
16. Fortugno P, Wall NR, Giodini A, et al. Surviivin exists in immuno-chemically distinct subcellular pools and is involved in spindle microtuble function. J Cell Sci, 2002, 115(4): 575-585
17. Li F, Ambrosini G, Chu EY, et al. Control of apoptosis and mitotic spindle checkpoint by survivin. Nature, 1998, 396(6711): 580-584.
1. Dykxhoorn DM, Novina CD, Sharp PA. Killing the messenger: short RNAs that silence gene expression. Nat Rev Mol Cell Biol, 2003, 4(6): 457-467.
2. Fire A, Xu S, Montgomery MK, et al. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature, 1998, 391(6669): 806-811.
3. Elbashir SM, Harborth J, Lendeckel W, et al. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature, 2001, 411(6836): 494-498.
4. Caplen NJ, Parrish S, Imani F, et al. Specific inhibition of gene expression by small double-stranded RNAs in invertebrate and vertebrate systems. Proc Natl Acad Sci U S A, 2001, 98(17): 9742-9747.
5. Brummelkamp TR, Bernards R, Agami R. A system for stable expression of short interfering RNAs in mammalian cells. Science, 2002, 296(5567): 550-553.
6. Lee NS, Dohjima T, Bauer G, et al. Expression of small interfering RNAs targeted against HIV-1 rev transcripts in human cells. Nat Biotechnol, 2002, 20(5): 500-505.
7. Yu JY, De Ruiter SL, Turner DL. RNA interference by expression of short-interfering RNAs and hairpin RNAs in mammalian cells. Proc Natl Acad Sci U S A. 2002, 99(9): 6047-6052.
8. Harmon GJ. RNA interference. Nature, 2002, 418(6894): 244-251.
9. Paddison PJ, Caudy AA, Hannon GJ. Stable suppression of gene expression by RNAi in mammalian cells. Proc Natl Acad Sci U S A, 2002, 99(3): 1443-1448.
10. Miyagishi M, Taira K. U6 promoter-driven siRNAs with four uridine 3' overhangs efficiently suppress targeted gene expression in mammalian cells. Nat Biotechnol, 2002, 20(5): 497-500.
11. Tuschl T, Zamore PD, Lehmann R, et al. Targeted mRNA degradation by double-stranded RNA in vitro. Genes Dev, 1999, 13(24): 3191-3197.
12. Elbashir SM, Lendeckel W, Tuschl1 T, et al. RNA interference is mediated by 21- and 22-nucleotide RNAs. Genes Dev, 2001, 15(2): 188-200.
13. Zhang L, Yang N, Mohamed-Hadley A, et al. Vector-based RNAi, a novel tool for isoform-specific knock-down of VEGF and anti-angiogenesis gene therapy of cancer. Biochem Biophys Res Commun, 2003, 303(4): 1169-1178.
14. Li K, Lin SY, Brunicardi FC, et al. Use of RNA interference to target cyclin E-overexpressing hepatocellular carcinoma. Cancer Res, 2003, 63(13):3593-3597.
15. Chen Y, Du D, Wu J, et al. Inhibition of hepatitis B virus replication by stably expressed shRNA. Biochem Biophys Res Commun, 2003, 311(2):398-404.
16. Kretschmer-Kazemi Far R, Sczakiel G. The activity of siRNA in mammalian cells is related to structural target accessibility: a comparison with antisense oligonucleotides. Nucleic Acids Res. 2003, 31 (15):4417-4424.
17. Bohula EA, Salisbury AJ, Sohail M, et al. The efficacy of small interfering RNAs targeted to the type 1 insulin-like growth factor receptor (IGF1R) is influenced by secondary structure in the IGF1R transcript. J Bio Chem, 2003, 278(18): 15991～15997
18. Lee NS, Dohjima T, Bauer G, et al. Expression of small interfering RNAs targeted against HIV-1 rev transcriptis in human cells. Nat Biotech, 2002, 20(5):500～505
19. Vickers TA, Koo S, Bennett CF et al. Efficient reduction of target RNAs by small interfering RNA and Rnase H2 dependent antisense agents. J Biol Chem, 2003, 278(9):7108～7118
20．夏云，林汝仙，郑素军等．靶向端粒酶逆转录酶(hTERT)RNAi载体的构建及活性评价．生物化学与生物物理进展．2004，31(12)：1079-1084
1. Bontenbal M, Nortier JW, Beex LV, et al. Adjuvant systemic therapy for patients with respectable breast cancer: guideline from the Dutch National Breast Cancer Plat form and the Dutch Society for Medical. Oncology Ned Tijdschr Geneeskd, 2000, 144(21):984-989.
2. Hussain SA, Palmer DH, Stevens A, et al. Role of chemotherapy in breast cancer. Expert Rev Anticancer Ther, 2005, 5(6): 1095-1110.
3. O'Shaughnessy J. Extending survival with chemotherapy in metastatic breast cancer. Oncologist, 2005; 10 Suppl 3:20-29.
4. Hait WN, Yang JM. Clinical management of recurrent breast cancer: development of multidrug resistance (MDR) and strategies to circumvent it. Semin Oncol, 2005, 32(6 Suppl 7):S16-21.
5. Lehnert M. Chemotherapy resistance in breast cancer. Anticancer Res, 1998, 18(3 C):2225-2226
6. Sun YL, Zhou GY, Li KN, Suppression of glucosylceramide synthase by RNA interference reverses multidrug resistance in human breast cancer cells. Neoplasma, 2006; 53(1):1-8.
7. Lopes de Menezes DE, Hu Y, Mayer LD. Combined treatment of Bcl-2 antisense oligodeoxynucleotides (G3139), p-glycoprotein inhibitor (PSC833), and sterically stabilized liposomal doxorubicin suppresses growth of drug-resistant growth of drug-resistant breast cancer in severely combined immunodeficient mice. J Exp Ther Oncol, 2003, 3(2):72-82.
8．吴二喜，印大中，王凤飞．核糖核酸干扰(RNAi)在生物医学研究中的应用．生命科学研究．2005，9(2)：95-98
9. Vickers TA, Koo S, Bennett CF et al. Efficient reduction of target RNAs by small interfering RNA and Rnase H2 dependent antisense agents. J Biol Chem, 2003, 278(9):7108～7118
10．夏云，林汝仙，郑素军等．靶向端粒酶逆转录酶(hTERT)RNAi载体的构建及活性评价．生物化学与生物物理进展．2004，31(12)：1079-1084
11. Zhang L, Yang N, Mohamed-Hadley A, et al. Vector-based RNAi, a novel tool for isoform-specific knock-down of VEGF and anti-angiogenesis gene therapy of cancer. Biochem Biophys Res Commun, 2003, 303(4): 1169-1178.
12. Tuschl T, Zamore PD, Lehmann R, et al. Targeted mRNA degradation by double-stranded RNA in vitro. Genes Dev, 1999, 13(24): 3191-3197.
13. Elbashir SM, Lendeckel W, Tuschl1 T, et al. RNA interference is mediated by 21-and 22-nucleotide RNAs. Genes Dev, 2001, 15(2): 188-200.
14. Miyagishi M, Taira K. U6 promoter-driven siRNAs with four uridine 3' overhangs efficiently suppress targeted gene expression in mammalian cells. Nat Biotechnol.2002, 20(5): 497-500.
15. Yu JY, De Ruiter SL, Turner DL. RNA interference by expression of short-interfering RNAs and hairpin RNAs in mammalian cells. Proc Natl Acad Sci U S A, 2002, 99(9): 6047-6052.
16. Scherr M, Morgan MA, Eder M. Gene silencing mediated by small interfering RNAs in mammalian cells. Curr Med Chem, 2003, 10(3): 245-256.
17. Lu SY, Sui YF, Li ZS, et al. Construction of a regulable gene therapy vector targeting for hepatocellular carcinoma. World J Gastroenterol, 2003, 9(4): 688-91.
18. O'Connell M J, Cimprich KA. G_2 damage checkpoints: what is the turn-on? J Cell Sci, 2005, 118(Pt 1): 1-6.
19. Zhou BB, Elledge SJ. The DNA damage response: putting checkpoints in perspective. Nature, 2000, 408(6811): 433-439.
20. Norbury CJ, Zhivotovsky B. DNA damage-induced apoptosis. Oncogene, 2004, 23(16): 2797-2808.
21. Dasika GK, Lin SC, Zhao S, et al. DNA damage-induced cell cycle checkpoints and DNA strand break repair in development and tumorigenesis. Oncogene, 1999, 18(55): 7883-7899.
22. Suzuki A, Ito T, Kawano H, et al. Survivin initiates procaspase 3/p21 complex formation as a result of interaction with Cdk4 to resist Fas-mediated cell death. Oncogene. 2000, 19(10): 1346-1353.
23. Shin S, Sung BJ, Cho YS, et al. An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and -7. Biochemistry, 2001, 40(4): 1117-1123.
24. Sugahara K, Uemura A, Harasawa H, et al. Clinical relevance of survivin as a biomarker in neoplasms, especially in adult T-cell leukemias and acute leukemias. Int J Hematol, 2004, 80(1): 52-58.
25. Kobayashi K, Hatano M, Otaki M, et al. Expression of a murine homologue of the inhibitor of apoptosis protein is related to cell proliferation. Proc Natl Acad Sci USA, 1999, 96(4): 1457-1462.
26. Fulda S, Debatin KM. Targeting apoptosis pathways in cancer therapy. Curr Cancer Drug Targets, 2004, 4(7): 569-576.
27. Stavrovskaya AA. Cellular mechanisms of multidrug resistance of tumor cells. Biochemistry (Mosc), 2000, 65(1): 95-106.
28. Reed JC. Apoptosis mechanisms: implications for cancer drug discovery. Oncology (Williston Park), 2004, 18(13 Suppl 10): 11-20.
29. Tamm I, Wang Y, Sausville E, et al. IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs. Cancer Res, 1998, 58(23): 5315-5320.
30. Nomura T, Yamasaki M, Nomura Y, et al. Expression of the inhibitors of apoptosis proteins in cisplatin-resistant prostate cancer cells. Oncol Rep, 2005, 14(4): 993-997
31. Notarbartolo M, Lo Cicero S, Meli M, et al. Induction of apoptosis by the adenosine derivative IB-MECA in parental or multidrug-resistant HL-60 leukemia cells: possible relationship to the effects on inhibitor of apoptosis protein levels. Chemotherapy, 2005, 51(5): 272-279.
32. Tarnawski A, Pai R, Chiou SK, et al. Rebamipide inhibits gastric cancer growth by targeting survivin and Aurora-B. Biochem Biophys Res Commun, 2005, 334(1): 207-212.
33. Zhang M, Mukherjee N, Bermudez RS, et al. Adenovirus-mediated inhibition of survivin expression sensitizes human prostate cancer cells to paclitaxel in vitro and in vivo. Prostate, 2005, 64(3): 293-302.
1. Anderson W F, Blaese R M, Culver K, et al. The ADA human gene therapy clinical protocol: points to consider response with clinical protocol. Hum Gene Ther, 1990, 1(3): 331～362
2. Edelstein ML, Abedi MR, Wixon J, et al. Gene therapy clinical trials worldwide 1989-2004-an overview. J Gene Med, 2004, 6(6): 597-602
3. Gura T. Hemophilia: after a setback, gene therapy progresses...gingerly. Science, 2001, 291 (5509): 1692～1697
4. Kohn D B, Sadelain M, Glorioso J C, et al. Occurrence of leukaemia following gene therapy of X-linked SCID. Nat Rev Cancer, 2003, 3(7):477～488
5. Marshall E. Gene therapy. Second child in French trial is found to have leukemia. Science, 2003, 299(5605): 320
6. Sadelain M. Insertional oncogenesis in gene therapy: how much of a risk? Gene Ther, 2004, 11(7): 569～573
7. Caplen N J, Parrish S, Imani F, et al. Proc Natl Acad Sci USA, 2001; 98: 9746～9747
8. Elbashir S M, Harborth J, Lendeckel W, et al. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature, 2001, 411 (6836): 494-498.
9. Martiniello-Wilks R, Dane A, Voeks DJ, et al. Gene-directed enzyme prodrug therapy for prostate cancer in a mouse model that imitates the development of human disease. J Gene Med, 2004, 6(1): 43-54.
10. Moon C, Oh Y, Roth JA. Current status of gene therapy for lung cancer and head and neck cancer. Clin Cancer Res, 2003, 9(14): 5055-67.
11. Sotomayor MG, Yu H, Antonia S, et al. Advances in gene therapy for malignant melanoma. Cancer Control, 2002, 9(1): 39-48.
12. Roth JA, Grammer SF, Swisher SG, et al. Gene therapy approaches for the management of non-small cell lung cancer. Semin Oncol, 2001, 28(4 Suppl 14): 50-56.
13. Asklund T, Appelskog IB, Ammerpohl O, et al. Gap junction-mediated bystander effect in primary cultures of human malignant gliomas with recombinant expression of the HSVtk gene. Exp Cell Res, 2003, 284(2): 185-195
14. Neijssen J, Herberts C, Drijfhout JW, et al. Cross-presentation by intercellular peptide transfer through gap junctions. Nature, 2005, 434(7029): 83-88.
15. Sanson M, Marcaud V, Robin E, et al. Connexin 43-mediated bystander effect in two rat glioma cell models. Cancer Gene Ther, 2002, 9(2): 149-155.
16. Howarth M, Elliott T. The processing of antigens delivered as DNA vaccines. Immunol Rev, 2004, 199: 27-39.
17. Carroll JL, Nielsen LL, Pruett SB, et al. The role of natural killer cells in adenovirus-mediated p53 gene therapy. Mol Cancer Ther, 2001, 1(1): 49-60.
18. Ray G, Banerjee S, Saxena NK, Stimulation of MCF-7 tumor progression in athymic nude mice by 17beta-estradiol induces WISP-2/CCN5 expression in xenografts: a novel signaling molecule in hormonal carcinogenesis. Oncol Rep, 2005, 13(3): 445-448.
19. Stephen R. D. Johnstonl, Irene M. Idoxifene antagonizes estradiol-dependent MCF-7 breast cancer xenograft growth through sustained induction of apoptosis. Cancer Res, 1999, 59(15): 3646-3651.
20. Motomura S, Motoji T, Takanashi M, et al. Inhibition of P-glycoprotein and recovery of drug sensitivity of human acute leukemic blast cells by multidrug resistance gene (mdr1) antisense oligonucleotides. Blood, 1998, 91(9): 3163-3171
21. Ren Y, Wei D, Zhan X. Inhibition of P-glycoprotein and increasing of drug-sensitivity of a human carcinoma cell line (KB-A-1) by an antisense oligodeoxynucleotide-doxorubicin conjugate in vitro. Biotechnol Appl Biochem, 2005, 41 (Pt 2): 137-143.
22. Ramachandran C, Wellham. Effect of MDR1 phosphorothioate antisense oligodeoxynucleotides in multidrug-resistant human tumor cell lines and xenografts. Anticancer Res, 2003, 23(3B): 2681-2690
23. Huesker M, Folmer Y, Schneider M, et al. Reversal of drug resistance of hepatocellular carcinoma cells by adenoviral delivery of anti-MDR1 ribozymes. Hepatology, 2002, 36(4 Pt 1): 874-884.
24. Nagata J, Kijima H, Hatanaka H, et al. Reversal of drug resistance using hammerhead ribozymes against multidrug resistance-associated protein and multidrug resistance 1 gene. Int J Oncol, 2002, 21(5):1021-1026.
25. Hua J, Mutch DG, Herzog TJ. Stable suppression of MDR-1 gene using siRNA expression vector to reverse drug resistance in a human uterine sarcoma cell line. Gynecol Oncol, 2005, 98(1):31-38.
26. Nieth C, Priebsch A, Stege A, et al. Modulation of the classical multidrug resistance (MDR) phenotype by RNA interference (RNAi). FEBS Lett, 2003, 545(2-3):144-150.
27. Kaufmann SH, Vaux DL. Alterations in the apoptotic machinery and their potential role in anticancer drug resistance. Oncogene, 2003, 22(47):7414-7430.
28. Davis JM, Navolanic PM, Weinstein-Oppenheimer CR, et al. Raf-1 and Bcl-2 induce distinct and common pathways that contribute to breast cancer drug resistance. Clin Cancer Res, 2003, 9(3): 1161-1170.
29. Williams J, Lucas PC, Griffith KA, et al. Expression of Bcl-xL in ovarian carcinoma is associated with chemoresistance and recurrent disease. Gynecol Oncol, 2005, 96(2):287-295.
30. Dai Y, Rahmani M, Corey SJ, et al. A Bcr/Abl-independent, Lyn-dependent form of imatinib mesylate (STI-571) resistance is associated with altered expression of Bcl-2. J Biol Chem, 2004, 279(33):34227-34239.
31．邓凯贤，钟玲，姜梅贤等．RNA干扰技术沉默survivin基因逆转卵巢癌细胞株SKOV3／ADM耐药性的研．中华妇产科杂志，2005，40(12)836-839
32. Zaffaroni N, Pennati M, Daidone MG. Survivin as a target for new anticancer interventions. J Cell Mol Med, 2005, 9(2):360-372.