RNA干扰TXR1基因对鼻咽癌细胞耐药的影响
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摘要
目的：探索TXR1基因在鼻咽癌紫杉醇耐药中的作用,利用RNA干扰技术抑制鼻咽癌紫杉醇耐药细胞CNE-1/Taxol的TXR1基因表达,同时研究TXR1基因的表达与鼻咽癌紫杉醇耐药的相关性。
方法：
1.通过脂质体介导转染siRNA至鼻咽癌紫杉醇耐药细胞株CNE-1/Taxol。
2.利用实时荧光定量RT-PCR. Western-blot方法分别检测RNA干扰前、后的鼻咽癌紫杉醇耐药CNE-1/Taxol细胞株的TXR1基因表达差异。
3.利用MTT实验检测TXR1基因表达抑制后的鼻咽癌紫杉醇耐药细胞CNE-1/Taxol的耐药性变化,观察TXR1基因在紫杉醇耐药过程中的作用。
结果：
1.针对TXR1基因的siRNA转染耐药细胞CNE-1/Taxol后,耐药细胞TXR1的mRNA及蛋白表达均明显下调。干扰组和阴性对照组的mRNA表达分别是脂质体组mRNA表达量的0.12±0.02倍、0.97±0.07倍,干扰组分别和阴性对照组、脂质体组比较,差异具有统计学意义(P<0.01)。干扰组、阴性对照组的蛋白表达量分别是脂质体组的0.36±0.07、1.02±0.03倍,干扰组与脂质体组、阴性对照组的蛋白表达相比较,差异有统计学意义(P<0.01)。
2.TXRl基因表达抑制后,CNE-1/Taxol对紫杉醇的敏感性显著增高,其IC50值降低了2.12倍,从而部分逆转CNE-1/Taxol耐药。
结论：
1.特异性siRNA分子能有效的抑制鼻咽癌紫杉醇耐药细胞的TXR1基因表达。
2.运用RNA干扰技术抑制TXR1基因可能部分逆转人鼻咽癌紫杉醇耐药细胞CNE-1/Taxol的耐药性。TXR1基因可能成为逆转鼻咽癌细胞紫杉醇耐药及肿瘤治疗的靶分子。
图7幅,表2个,参考文献53篇
Objectives:To explore the role of TXR1played in taxol resistance of nasopharyngeal carcinoma, the expression of TXR1genes was kocked down by RNA interference in paclitaxel resisitant cells of nasopharyngeal carcinoma, and the correlation was analyzed between the expression of TXR1genes and paclitaxel resistance.
Methods:
1.TXR1siRNA was transfected into the NPC CNE-1/Taxol cells by using liposomes2000.
2. The expressional change of both TXR1mRNA and protein was detected by real time RT-PCR and western blot, respectively.
3. Proliferation inhibition rate of CNE-1/Taxol cells was assayed by MTT in drug-resistant NPC cells.
Results:
1. The TXR1-targeted siRNA can effectively decrease the expression level of TXR1gene mRNA and protein in NPC cells.
2. The sensitivity to paclitaxel of CNE-1/Taxol was significantly increased after inhibition of TXR1gene expression by siRNA technology, and a2.12-fold decease was observed in its IC50value.
Conclusion:
1. The siRNA can effectively decrease the mRNA and protein expression level of TXR1gene in nasopharyngeal carcinoma cells, and increase the sensitivity to paclitaxel in CNE-1/Taxol, and reverse the drug resistance.
2. The results indicated that the TXR1gene is one of the important target molecules in the reversion of the paclitaxel-resistance in nasopharyngeal carcinoma cells.
方法：
1.通过脂质体介导转染siRNA至鼻咽癌紫杉醇耐药细胞株CNE-1/Taxol。
2.利用实时荧光定量RT-PCR. Western-blot方法分别检测RNA干扰前、后的鼻咽癌紫杉醇耐药CNE-1/Taxol细胞株的TXR1基因表达差异。
3.利用MTT实验检测TXR1基因表达抑制后的鼻咽癌紫杉醇耐药细胞CNE-1/Taxol的耐药性变化,观察TXR1基因在紫杉醇耐药过程中的作用。
结果：
1.针对TXR1基因的siRNA转染耐药细胞CNE-1/Taxol后,耐药细胞TXR1的mRNA及蛋白表达均明显下调。干扰组和阴性对照组的mRNA表达分别是脂质体组mRNA表达量的0.12±0.02倍、0.97±0.07倍,干扰组分别和阴性对照组、脂质体组比较,差异具有统计学意义(P<0.01)。干扰组、阴性对照组的蛋白表达量分别是脂质体组的0.36±0.07、1.02±0.03倍,干扰组与脂质体组、阴性对照组的蛋白表达相比较,差异有统计学意义(P<0.01)。
2.TXRl基因表达抑制后,CNE-1/Taxol对紫杉醇的敏感性显著增高,其IC50值降低了2.12倍,从而部分逆转CNE-1/Taxol耐药。
结论：
1.特异性siRNA分子能有效的抑制鼻咽癌紫杉醇耐药细胞的TXR1基因表达。
2.运用RNA干扰技术抑制TXR1基因可能部分逆转人鼻咽癌紫杉醇耐药细胞CNE-1/Taxol的耐药性。TXR1基因可能成为逆转鼻咽癌细胞紫杉醇耐药及肿瘤治疗的靶分子。
图7幅,表2个,参考文献53篇
Objectives:To explore the role of TXR1played in taxol resistance of nasopharyngeal carcinoma, the expression of TXR1genes was kocked down by RNA interference in paclitaxel resisitant cells of nasopharyngeal carcinoma, and the correlation was analyzed between the expression of TXR1genes and paclitaxel resistance.
Methods:
1.TXR1siRNA was transfected into the NPC CNE-1/Taxol cells by using liposomes2000.
2. The expressional change of both TXR1mRNA and protein was detected by real time RT-PCR and western blot, respectively.
3. Proliferation inhibition rate of CNE-1/Taxol cells was assayed by MTT in drug-resistant NPC cells.
Results:
1. The TXR1-targeted siRNA can effectively decrease the expression level of TXR1gene mRNA and protein in NPC cells.
2. The sensitivity to paclitaxel of CNE-1/Taxol was significantly increased after inhibition of TXR1gene expression by siRNA technology, and a2.12-fold decease was observed in its IC50value.
Conclusion:
1. The siRNA can effectively decrease the mRNA and protein expression level of TXR1gene in nasopharyngeal carcinoma cells, and increase the sensitivity to paclitaxel in CNE-1/Taxol, and reverse the drug resistance.
2. The results indicated that the TXR1gene is one of the important target molecules in the reversion of the paclitaxel-resistance in nasopharyngeal carcinoma cells.
引文
[1]Fandi A, Altume M, Azli N, et al. Nasopharyngeal cancer:epidemiology, staging and treatment[J].Semin oncol,1994,21 (3):382-397.
[2]Jeannel D,Bouvier QHuber A.Nasopharyngeal carcinoma:an epidemical approach carcinogenesis[J].Cancer Suv.1999.33:125-155.
[3]Zhengrong Wu, Gang Li, Lirong Wu, et al. Cripto-1 overexpression is involved in the tumorigenesis of nasopharyngeal carcinoma[J]. BMC Cancer,2009, 315(9):1-14.
[4]Cheng SH, et al. Concomitant radiotherapy and chemotherapy for early stage nasopharyngeal carcinoma[J]. Clin Oncol 2000,18:2040-2045.
[5]Serin M, et al. Radiation therapy and concurrent cisplatin in management of locoregionally advanced nasopharyngeal carcinomas[J]. Acta Oncology 1999, 38:1031-1035.
[6]Cheng SH, Tsai sv,Yen KL etal. Concomitant radiotherapy and chemotherapy for early-stage nasopharyngeal carcinoma[J].Clin Oncol 2000,18(10):2040-2045.
[7]Serin M, Erkal HS, etal. Radiation theraphy and concurrent cisplatin in management of locoregionally advanced nasopharyneal carcinomas [J].Acta Oncol 1999,38(8):1031-1035.
[8]肖崇厚.中药化学[M].上海：上海科学技术出版社,1997：461-463.
[9]Wani MC,Taylor HL.Wall ME,etal.Plant antitumor agents Ⅵ.The isolation and structure of Taxol.a novel antileukemic and anti.tumor agent from Taxus brevifolia[J].Am Chem SOC,1971,93(9):2325-2327.
[10]Sparano JA, Wang M, Martino S, et al. Weekly paclitaxel in the adjuvant treatment of breast cancer[J]. N Engl J Med,2008,358(16):1663-1671.
[11]万云峰,姚明辉.紫杉醇耐药机制的研究进展[J].国外医药.合成药、生化药、制剂分册,2002,(23)3：132-134.
[12]张力,姜文奇.紫杉醇(Paelitaxel)治疗晚期鼻咽癌的临床研究[J].癌症.2000,(8)：811-813.
[13]Holmes FA, Waiters RS, Theriault RL, et al. Phase II Trial of Taxol, an Active Drug in the Treatment ofMetastatic Breast Cancer[J].Natl. Cancer Inst.1991, 83(24):1797-1805.
[14]Holmes FA,Waiters RS,Theriault RL,et al.Phase II Trial of Taxol,an Active Drug in the Treatment of Metastatic Breast Cancer[J].Natl.Cancer Inst.1991. 83(24):1797-1805.
[15]Gillet JP,Efferth T,Steinbach D,et al. Mieroarray-based detection Of multidrug resistance in human tumor cells by expression profiling of ATP-binding cassette transporter genes[J]. Cancer Res.2004Dec 15:64(24):8987-93.
[16]Takashi Nakamuraa, Mikio Okaa,1, Kikuo Aizawab.Direct Interaction between a Quinoline Derivative, MS-209, and Multidrug Resistance Protein (MRP) in Human Gastric Cancer Cells [J].Biochemical and Biophysical Research Communications.1995;92:7690.
[17]Johnatty SE, Beesley J, Paul J, et aL ABCB1(MDR I)polymorphisms and progression-free survival among women with ovarian cancer following paclitaxel/carboplatin chemotherapy[J].Clin Cancer Res,2008,14(17):5594-5601.
[18]Noguchi K, Kawahara H, Kaji A, et aL Substrate dependent bidirectional modulation of P-glyeoprotein-mediated drug resistance by erlotinib[J].Cancer Sci,2009,100(9):1701-1707.
[19]Lih CJ, Wei W, Cohen SN. TXR1:transcriptional regulator of thrombospondin-1 that modulates cellular sensitivity to taxanes[J]. Genes Dev, 2006,20:2082-95.
[20]Amerongen RV, Bern A. TXR1-mediated thrombospondin repression:a novel mechanism of resistance to taxanes [J].Genes Dev,2006,20:1975-81.
[21]杨纯正.肿瘤细胞耐药基因研究进展[J].中国肿瘤,1996,5(7)：15.
[22]Fire A, Xu S, Montgomery M, Kostas S, Driver S, Mello C. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans[J]. Nature.1998,391 (6669):806-11.
[23]Jae-Yean, Kim. Regulation of short-distance transport of RNA and protein. Current Opinion in Plant Biology [J].February 2005,8:45.
[24]NJ Caplen, J Fleenor, A Fire, RA Morgan. dsRNA-mediated gene silencing in cultured Drosophila cells:a tissue culture model for the analysis of RNA interference[J].Gene,2000;252:95-105.
[25]Waterhouse PM, Graham MW, Wang MB. Virus resistance and gene silencing in plants can be induced by simultaneous expression of sense and antisense RNA[J].Proc Natl Acad Sci USA 1998;95:13959-13964.
[26]SM Elbashir, J Harborth, W Lendeckel, A Yalcin.Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells[J].nature, 2001;411:494-498.
[27]Cogoni C, Macino G. Gene silencing in Neurospora crassa requires a Protein homologous to RNA-dependent RNA polymerase[J].Nature 1999; 399: 166-169.
[28]Baulcombe DC, Voinnet O. Systemic signalling in gene silencing[J].Nature. 1997,389 (6651):553.
[29]David C. Baulcombe, Andrew J. Hamilton. A Species of Small Antisense RNA in Posttranscriptional Gene Silencing in Plants[J].Science.1999,286 (5441): 950-952.
[30]Caudy AA, Bernstein E; Hammond SM, Hannon GJ. Role for a bidentate ribonuclease in the initiation step of RNA interference[J].Nature.2001,409 (1818): 363-6.
[31]Vickers TA, Koo S, Bennett CF, et al. Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. A comparative analysis [J]. J Biol Chem,2003,278(9):7108-7118.
[32]H Xia, Q Mao, SL Eliason, SQ Harper, IH Martins.RNAi suppresses polyglutamine-induced neurodegeneration in a model of spinocerebellar ataxia[J].Nature medicine,2004; 10:816-820.
[33]Liang W, Zhang WJ, Gao QM, et al. Silencing of survivin gene in jeko-1 cell line with small interfering RNA [J]. Zhongguo Shi YanXue Ye Xue Za Zhi, 2012,20(1):88-92.
[34]Caldas H,Holloway MP,Hall BM,et al. Survivin-directed RNA Interference cocktail is a potent suppressor of tumor growth in vivo [J].Med Genet,2006,43(2): 119-128.
[35]Yuan J,Kramer A,Matthess Y,et al.Stable gene silencing of cyelin Bl in tumor cells increase susceptibility to taxo land leads to growth arrest in vivo[J]. Oncogene,2006,25(12):1753-1762.
[36]Zou W,Yang H,Hou XH,et al.Inhibition of CD 147 gene expression Via RNA interference reduces tumor cell invasion, tumorigenicity and increases chemosensitivity to paclitaxel in H0-8910pm cells[J]. Cancer Lett,2007,248(2) 211-218.
[37]Garcia-Martin, et al. Acquired resistance to the anticancer drug paclitaxel is associated with induction of cytochrome P450 2C8[J].Pharmacogenomics 2006,7: 575-85.
[38]Rappa G et al. New insights into the biology and pharmacology of the multidrug resistance protein(MRP)from gene knockout models[J].Biochem Pharmaco1.1999,58(4):557-62.
[39]HUTVAGNER G, ZAMORE P D. RNAi:nature abhors adouble-strand[J]. Curt Opin Genet Dev,2002,12:225-232.
[40]Fire A, Xu S, Montgomery MK, Kostas SA, et al. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature, 1998;19;391(6669):806-811.
[41]Caudy AA, Bernstein E; Hammond SM, Hannon GJ. Role for a bidentate ribonuclease in the initiation step of RNA interference[J]. Nature.2001,409 (1818): 363-6.
[42]Zamore PD, Tuschl T, Shaw PA,et al. RNAi:double2stranded RNA direct the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals[J].Cell,2000, 101(1):25-33.
[43]Jae-Yean, Kim. Regulation of short-distance transport of RNA and protein. Current Opinion in Plant Biology [J].February 2005,8:45.
[44]Kurreck J.RNA interference:from basic research to therapeutic applications [J]. Angew Chem Int Ed En91.2009,48(8):1378-1398.
[45]Nieth C, Priebsch AStege A et al. Modulation of the classicalmulti-drug resistance(MDR)phenotype by RNA interference(RNAi) [J].FEBS Lett,2003, 545(2-3):144-150.
[46]Liang W, Zhang WJ, Gao QM, et al. Silencing of survivin gene in jeko-1 cell line with small interfering RNA[J].Zhongguo Shi YanXue Ye Xue Za Zhi,2012, 20(1):88-92.
[47]Papadaki C, Mavroudis D, Trypaki M, et al. Tumoral expression of TXR1 and TSP1 predicts overall survival of patients with lung adenocarcinoma treated with first-line docetaxel-gemcitabine regimen[J]. Clin Cancer Res,2009,15(11):3827-3833.
[48]Cardone L,de Cristofaro T,Affaitati A,et al.A-kinase anchor protein 84/121 are targeted to mitochondria and mitotic spindles by overlapping amino-terminal motifs [J]. Mol Biol,2002,320(3):663.
[49]Zhi-Gang BAI,XIANG QU,WEI HAN,XUE-MEI MA and ZHONG-TAO ZHANG, et al. Expression of taxol resistance gene 1 correlates with gastric cancer patient clinical outcome and induces taxol resistance[J].Molecular Medicine REPORTS 2010,3:1071-1078.
[50]马雪梅,白志刚,张忠涛,等.紫杉醇对乳腺癌细胞紫杉醇耐药基因TXR1表达的影响[J].中国医药生物技术,2010,05(6)：429-433.
[51]Ferguson T, Wilcken N, Vagg R, et al. Taxanes for adjuvant treatment of early breast cancer[J]. Cochrane Database Syst Rev,2007,(4):CD004421.
[52]Kutuk O, Letai A. Alteration of the mitochondrial apoptotic pathway is key to acquired paclitaxel resistance and can be reversed byABT-737[J]. Cancer Res,2008, 68(19):7985-7994.
[53]马雪梅,白志刚,张忠涛,等.紫杉醇耐药基因TXRl对乳腺癌细胞耐药性的影响[J].中国肿瘤临床,2010,12(6)：1205-1208.
[1]杨纯正.肿瘤细胞耐药基因研究进展[J].中国肿瘤,1996,5(7)：15.
[2]Lih CJ, Wei W, Cohen SN. TXR1:transcriptional regulator of thrombospondin-1 that modulates cellular sensitivity to taxanes[J]. Genes Dev. 2006,20:2082-95.
[3]Amerongen RV, Bern A. TXR1-mediated thrombospondin repression:a novel mechanism of resistance to taxanes [J].Genes Dev.2006,20:1975-81.
[4]Tas F, Duranyildiz D, SoydincHO, el al. Effect of maximum. Toleratod doses and low-dose metronomic chemotherapy on serum vascular endothelial growth factor and thrombospondin-1 levels in patients with advanced nonsmall cell lung cancer[J]. Cancer Chemother pharmacol,2008.61(5):721-725.
[5]Shingyoji M, Ando S, Nishimura H, el aL VEGF in patients with non-gmall cell lung cancer during combination chemotherapy of carboplatin and paclitaxel Anticancer Res,2009,29(7):2635-2639.
[6]Yoo GH, Lin 1-IS。 lskander AJ, et aL Docelaxel associated pathways in cisplatin resistant head and neck squamous cell carcinoma:a pilot study[J]. Laryngoscope,2005,115(11):1938-1946.
[7]Guerrero D;Guarch R;Ojer A Hypermethylation of the thrombospondin-1 gene is associated with poor prognosis in penile squamous cell carcinoma 2008(06).
[8]Punekar S, Zak S, If,alter VC, et al. Thrombospondin 1 and its mimerle peptide ABT-510 decrease angiogoncsis and inflammation in a routine model of inflammatory bowel disease[J]. Pathobiolngy,2008,75(1):9-21.
[9]Fraipont F.Nicholson AC,Feige JJ,et al. Thrombospondins and tumor angiogenesis Trends [J]. Mol Med,2001,7:401-407.
[10]Damber JE, Vallbo C, A]bertason P, el al. The anti-tumour effect of low-dose continuous chemotherapy may partly be mediated by thrombospoudin[J]. Cancer Chemother Phannacel,2006,58(3):354-360.
[11]Fraipont F.Nicholson AC,Feige JJ,et al. Thrombospondins and tumor angiogenesis Trends Mol Med,2001,7:401-407.
[12]Linda S, Gutierrez. The Role of Thrombospondin 1 on Intestinal Inflammation and Carcinogenesis[J]. Biomark Insights,2008,2008(3):171-178.
[13]Guerrero D, Guarch R, Ojer A, et al. Hypermethylation of the thrombospondin-1 gene is associated with poor prognosis in penile squamous cell carcinoma[J]. BJU Int,2008,102(6):747-755.
[14]Amerongen RV, Bern A. TXR1-mediated thrombospondin repression:a novel mechanism of resistance to taxanes [J].Genes Dev.2006,20:1975-81.
[15]Sparano JA, Wang M, Martino S, et al. Weekly paclitaxel in the adjuvant treatment of breast cancer[J]. N Engl J Med,2008,358(16):1663-1671.
[16]Ferguson T, Wilcken N, Vagg R, et al. Taxanes for adjuvant treatment of early breast cancer [J]. Cochrane Database Syst Rev,2007,(4):CD004421.
[17]Kutuk O, Letai A. Alteration of the mitochondrial apoptotic pathway is key to acquired paclitaxel resistance and can be reversed byABT-737[J]. Cancer Res, 2008,68(19):7985-7994.
[18]Kumar A,Soprano DR,Parekh HK. Cross-resistance to the synthetic Retinoid CD437 in a paclitaxel-resistant human ovarian carcinoma Cell line is independent of the overexpression of retinoic acid Receptor-gamma[J]. Cancer Res.2001 Oct 15;61(20):7552-5.
[19]Hudis C, Dang C. The taxane limbo:how low can we go? [J].Natl Cancer Inst,2008,100(11):761-763.
[20]彭小伟,谭国林.基因芯片技术检测鼻咽癌紫杉醇耐药及耐药逆转相关基因的表达[D].中南大学学报2012,37(1)48-52.
[21]Gillet JP,Efferth T,Steinbach D,et al. Mieroarray-based detection Of multidrug resistance in human tumor cells by expression profiling of ATP-binding cassette transporter genes[J]. Cancer Res.2004Dec15:64(24):8987-93.
[22]Takashi Nakamuraa, Mikio Okaa,1, Kikuo Aizawab.Direct Interaction between a Quinoline Derivative, MS-209, and Multidrug Resistance Protein (MRP) in Human Gastric Cancer Cells[J].Biochemical and Biophysical Research Communications.1995;92:7690.
[23]Johnatty SE, Beesley J, Paul J, et aL ABCB1(MDR I)polymorphisms and progression-free survival among women with ovarian cancer following paclitaxel/ carboplatin chemotherapy[J].Clin Cancer Res,2008,14(17):5594-5601.
[24]Noguchi K, Kawahara H, Kaji A, et aL Substrate · dependent bidirectional modulation of P-glyeoprotein-mediated drug resistance by erlotinib[J].Cancer Sci,2009,100(9):1701-1707.
[25]S Rao, N E Krauss, J M Heerding, C S Swindell, I Ringel, G A Orr and S B Horwitz. Ea al.3'-(p-azidobenzamido)taxol photolabels the N-terminal 31 amino acids of beta-tubulin[J] Journal of Biological,1994;269:3132.
[26]Preisler VK,Wuck D,Stoppe rH,et al.Combination of paclitaxel and radiation:genotoxicity in vitro in four mammalian cell lines[J]. Cancer Lett,1999, 145(1-2):29-33.
[27]Rowinsky EK, Donehower RC. Paclitaxel (taxol)[J]. N Engl J Med,1995, 332(15):1004-1014.
[28]Hutchinson E, A taxing problem [J]. Nat Rev Cancer,2006,6(8):578-579.
[29]Azuma K, Sasada T, Kawahara A, el aL Expression of ERCCI and class Ⅱbeta-tubulin in non-small cell lung cancer patients treated with carboplatin and paclitaxeL Lung Cancer[J].2009,64(3):326-333.
[30]Sere P, Reiman T, Lai R, el aL ClassⅢbeta-tubulin is a marker of paclitaxel resistance in carcinoma of unknown primary site[J].Cancer Chemother Pharmacol, 2007, (6):27-34.
[31]Aoki D, Oda Y, Hattori S, et aL Overexpression of class Ⅲ beta-tubulin predicts good response to taxane-based chemotherapy in ovarian dear cell adenocarcinoma[J].Clin Cancer Res,2009,15(4):1473.1480.
[32]Giannakakou P, SackeA D,L Rang. Y-K,Zhan. Z,Butcrs. J T M,Fojo. T,and Poruchynsky. M.S.Paclitaxel-resistant human ovarian cancer cells have mutant β-tuhulins that exhibit impaired paclitaxel-driven polymerization.[J].Biol. Chem.,272: 17118-17125.1997.
[33]马雪梅,白志刚,张忠涛,等.紫杉醇对乳腺癌细胞紫杉醇耐药基因TXR1表达的影响[J].中国医药生物技术,2010,05(6)：429-433.
[34]马雪梅,白志刚,张忠涛,等.紫杉醇耐药基因TXR1对乳腺癌细胞耐药性的影响[J].中国肿瘤临床,2010,12(6)：1205-1208.
[35]Papadaki C, Mavroudis D, Trypaki M, et al. Tumoral expression of TXR1 and TSP1 predicts overall survival of patients with lung adenocarcinoma treated with first-line docetaxel-gemcitabine regimen[J]. Clin Cancer Res,2009,15(11):3827-3833.
[36]J Souglakos, C Papadaki, et al. Correlation of BRCA1, TXR1 and TSP1 mRNA expression with treatment outcome to docetaxel-based first-line chemotherapy in patients with advanced/metastatic non-small-cell lung cancer[J]. British Journal of Cancer (2011) 104,316-323.
[37]Peng X, Li W, Tan G, et al. Reversal of taxol resistance by cisplatin in nasopharyngeal carcinoma by upregulating thromspondin-1 expression[J]. Anticancer Drugs.2010 Apr;21(4):381-8.
[38]余情杰.TXR1基因在鼻咽癌紫杉醇耐药细胞系中的表达[D].中南大学,2012,5(7)：15-48.
[39]Zhi-Gang BAI,XIANG QU,WEI HAN,XUE-MEI MA and ZHONG-TAO ZHANG, et al. Expression of taxol resistance gene 1 correlates with gastric cancer patient clinical outcome and induces taxol resistance[J].Molecular Medicine REPORTS 2010,3:1071-1078.
[40]姚晓峰.TXR1和TSP1在头颈部鳞癌中表达与紫杉醇耐药相关性的研究[J].2011国际暨全国头颈肿瘤学术大会论文集目录,中国,杭州,342-348.
[41]孙高英,王小元,张晓金.N-乙酰半胱氨酸对子宫颈癌细胞紫杉醇耐药性的影响[J].山东大学学报,2013,3(51)：42-47.
[2]Jeannel D,Bouvier QHuber A.Nasopharyngeal carcinoma:an epidemical approach carcinogenesis[J].Cancer Suv.1999.33:125-155.
[3]Zhengrong Wu, Gang Li, Lirong Wu, et al. Cripto-1 overexpression is involved in the tumorigenesis of nasopharyngeal carcinoma[J]. BMC Cancer,2009, 315(9):1-14.
[4]Cheng SH, et al. Concomitant radiotherapy and chemotherapy for early stage nasopharyngeal carcinoma[J]. Clin Oncol 2000,18:2040-2045.
[5]Serin M, et al. Radiation therapy and concurrent cisplatin in management of locoregionally advanced nasopharyngeal carcinomas[J]. Acta Oncology 1999, 38:1031-1035.
[6]Cheng SH, Tsai sv,Yen KL etal. Concomitant radiotherapy and chemotherapy for early-stage nasopharyngeal carcinoma[J].Clin Oncol 2000,18(10):2040-2045.
[7]Serin M, Erkal HS, etal. Radiation theraphy and concurrent cisplatin in management of locoregionally advanced nasopharyneal carcinomas [J].Acta Oncol 1999,38(8):1031-1035.
[8]肖崇厚.中药化学[M].上海：上海科学技术出版社,1997：461-463.
[9]Wani MC,Taylor HL.Wall ME,etal.Plant antitumor agents Ⅵ.The isolation and structure of Taxol.a novel antileukemic and anti.tumor agent from Taxus brevifolia[J].Am Chem SOC,1971,93(9):2325-2327.
[10]Sparano JA, Wang M, Martino S, et al. Weekly paclitaxel in the adjuvant treatment of breast cancer[J]. N Engl J Med,2008,358(16):1663-1671.
[11]万云峰,姚明辉.紫杉醇耐药机制的研究进展[J].国外医药.合成药、生化药、制剂分册,2002,(23)3：132-134.
[12]张力,姜文奇.紫杉醇(Paelitaxel)治疗晚期鼻咽癌的临床研究[J].癌症.2000,(8)：811-813.
[13]Holmes FA, Waiters RS, Theriault RL, et al. Phase II Trial of Taxol, an Active Drug in the Treatment ofMetastatic Breast Cancer[J].Natl. Cancer Inst.1991, 83(24):1797-1805.
[14]Holmes FA,Waiters RS,Theriault RL,et al.Phase II Trial of Taxol,an Active Drug in the Treatment of Metastatic Breast Cancer[J].Natl.Cancer Inst.1991. 83(24):1797-1805.
[15]Gillet JP,Efferth T,Steinbach D,et al. Mieroarray-based detection Of multidrug resistance in human tumor cells by expression profiling of ATP-binding cassette transporter genes[J]. Cancer Res.2004Dec 15:64(24):8987-93.
[16]Takashi Nakamuraa, Mikio Okaa,1, Kikuo Aizawab.Direct Interaction between a Quinoline Derivative, MS-209, and Multidrug Resistance Protein (MRP) in Human Gastric Cancer Cells [J].Biochemical and Biophysical Research Communications.1995;92:7690.
[17]Johnatty SE, Beesley J, Paul J, et aL ABCB1(MDR I)polymorphisms and progression-free survival among women with ovarian cancer following paclitaxel/carboplatin chemotherapy[J].Clin Cancer Res,2008,14(17):5594-5601.
[18]Noguchi K, Kawahara H, Kaji A, et aL Substrate dependent bidirectional modulation of P-glyeoprotein-mediated drug resistance by erlotinib[J].Cancer Sci,2009,100(9):1701-1707.
[19]Lih CJ, Wei W, Cohen SN. TXR1:transcriptional regulator of thrombospondin-1 that modulates cellular sensitivity to taxanes[J]. Genes Dev, 2006,20:2082-95.
[20]Amerongen RV, Bern A. TXR1-mediated thrombospondin repression:a novel mechanism of resistance to taxanes [J].Genes Dev,2006,20:1975-81.
[21]杨纯正.肿瘤细胞耐药基因研究进展[J].中国肿瘤,1996,5(7)：15.
[22]Fire A, Xu S, Montgomery M, Kostas S, Driver S, Mello C. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans[J]. Nature.1998,391 (6669):806-11.
[23]Jae-Yean, Kim. Regulation of short-distance transport of RNA and protein. Current Opinion in Plant Biology [J].February 2005,8:45.
[24]NJ Caplen, J Fleenor, A Fire, RA Morgan. dsRNA-mediated gene silencing in cultured Drosophila cells:a tissue culture model for the analysis of RNA interference[J].Gene,2000;252:95-105.
[25]Waterhouse PM, Graham MW, Wang MB. Virus resistance and gene silencing in plants can be induced by simultaneous expression of sense and antisense RNA[J].Proc Natl Acad Sci USA 1998;95:13959-13964.
[26]SM Elbashir, J Harborth, W Lendeckel, A Yalcin.Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells[J].nature, 2001;411:494-498.
[27]Cogoni C, Macino G. Gene silencing in Neurospora crassa requires a Protein homologous to RNA-dependent RNA polymerase[J].Nature 1999; 399: 166-169.
[28]Baulcombe DC, Voinnet O. Systemic signalling in gene silencing[J].Nature. 1997,389 (6651):553.
[29]David C. Baulcombe, Andrew J. Hamilton. A Species of Small Antisense RNA in Posttranscriptional Gene Silencing in Plants[J].Science.1999,286 (5441): 950-952.
[30]Caudy AA, Bernstein E; Hammond SM, Hannon GJ. Role for a bidentate ribonuclease in the initiation step of RNA interference[J].Nature.2001,409 (1818): 363-6.
[31]Vickers TA, Koo S, Bennett CF, et al. Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. A comparative analysis [J]. J Biol Chem,2003,278(9):7108-7118.
[32]H Xia, Q Mao, SL Eliason, SQ Harper, IH Martins.RNAi suppresses polyglutamine-induced neurodegeneration in a model of spinocerebellar ataxia[J].Nature medicine,2004; 10:816-820.
[33]Liang W, Zhang WJ, Gao QM, et al. Silencing of survivin gene in jeko-1 cell line with small interfering RNA [J]. Zhongguo Shi YanXue Ye Xue Za Zhi, 2012,20(1):88-92.
[34]Caldas H,Holloway MP,Hall BM,et al. Survivin-directed RNA Interference cocktail is a potent suppressor of tumor growth in vivo [J].Med Genet,2006,43(2): 119-128.
[35]Yuan J,Kramer A,Matthess Y,et al.Stable gene silencing of cyelin Bl in tumor cells increase susceptibility to taxo land leads to growth arrest in vivo[J]. Oncogene,2006,25(12):1753-1762.
[36]Zou W,Yang H,Hou XH,et al.Inhibition of CD 147 gene expression Via RNA interference reduces tumor cell invasion, tumorigenicity and increases chemosensitivity to paclitaxel in H0-8910pm cells[J]. Cancer Lett,2007,248(2) 211-218.
[37]Garcia-Martin, et al. Acquired resistance to the anticancer drug paclitaxel is associated with induction of cytochrome P450 2C8[J].Pharmacogenomics 2006,7: 575-85.
[38]Rappa G et al. New insights into the biology and pharmacology of the multidrug resistance protein(MRP)from gene knockout models[J].Biochem Pharmaco1.1999,58(4):557-62.
[39]HUTVAGNER G, ZAMORE P D. RNAi:nature abhors adouble-strand[J]. Curt Opin Genet Dev,2002,12:225-232.
[40]Fire A, Xu S, Montgomery MK, Kostas SA, et al. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature, 1998;19;391(6669):806-811.
[41]Caudy AA, Bernstein E; Hammond SM, Hannon GJ. Role for a bidentate ribonuclease in the initiation step of RNA interference[J]. Nature.2001,409 (1818): 363-6.
[42]Zamore PD, Tuschl T, Shaw PA,et al. RNAi:double2stranded RNA direct the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals[J].Cell,2000, 101(1):25-33.
[43]Jae-Yean, Kim. Regulation of short-distance transport of RNA and protein. Current Opinion in Plant Biology [J].February 2005,8:45.
[44]Kurreck J.RNA interference:from basic research to therapeutic applications [J]. Angew Chem Int Ed En91.2009,48(8):1378-1398.
[45]Nieth C, Priebsch AStege A et al. Modulation of the classicalmulti-drug resistance(MDR)phenotype by RNA interference(RNAi) [J].FEBS Lett,2003, 545(2-3):144-150.
[46]Liang W, Zhang WJ, Gao QM, et al. Silencing of survivin gene in jeko-1 cell line with small interfering RNA[J].Zhongguo Shi YanXue Ye Xue Za Zhi,2012, 20(1):88-92.
[47]Papadaki C, Mavroudis D, Trypaki M, et al. Tumoral expression of TXR1 and TSP1 predicts overall survival of patients with lung adenocarcinoma treated with first-line docetaxel-gemcitabine regimen[J]. Clin Cancer Res,2009,15(11):3827-3833.
[48]Cardone L,de Cristofaro T,Affaitati A,et al.A-kinase anchor protein 84/121 are targeted to mitochondria and mitotic spindles by overlapping amino-terminal motifs [J]. Mol Biol,2002,320(3):663.
[49]Zhi-Gang BAI,XIANG QU,WEI HAN,XUE-MEI MA and ZHONG-TAO ZHANG, et al. Expression of taxol resistance gene 1 correlates with gastric cancer patient clinical outcome and induces taxol resistance[J].Molecular Medicine REPORTS 2010,3:1071-1078.
[50]马雪梅,白志刚,张忠涛,等.紫杉醇对乳腺癌细胞紫杉醇耐药基因TXR1表达的影响[J].中国医药生物技术,2010,05(6)：429-433.
[51]Ferguson T, Wilcken N, Vagg R, et al. Taxanes for adjuvant treatment of early breast cancer[J]. Cochrane Database Syst Rev,2007,(4):CD004421.
[52]Kutuk O, Letai A. Alteration of the mitochondrial apoptotic pathway is key to acquired paclitaxel resistance and can be reversed byABT-737[J]. Cancer Res,2008, 68(19):7985-7994.
[53]马雪梅,白志刚,张忠涛,等.紫杉醇耐药基因TXRl对乳腺癌细胞耐药性的影响[J].中国肿瘤临床,2010,12(6)：1205-1208.
[1]杨纯正.肿瘤细胞耐药基因研究进展[J].中国肿瘤,1996,5(7)：15.
[2]Lih CJ, Wei W, Cohen SN. TXR1:transcriptional regulator of thrombospondin-1 that modulates cellular sensitivity to taxanes[J]. Genes Dev. 2006,20:2082-95.
[3]Amerongen RV, Bern A. TXR1-mediated thrombospondin repression:a novel mechanism of resistance to taxanes [J].Genes Dev.2006,20:1975-81.
[4]Tas F, Duranyildiz D, SoydincHO, el al. Effect of maximum. Toleratod doses and low-dose metronomic chemotherapy on serum vascular endothelial growth factor and thrombospondin-1 levels in patients with advanced nonsmall cell lung cancer[J]. Cancer Chemother pharmacol,2008.61(5):721-725.
[5]Shingyoji M, Ando S, Nishimura H, el aL VEGF in patients with non-gmall cell lung cancer during combination chemotherapy of carboplatin and paclitaxel Anticancer Res,2009,29(7):2635-2639.
[6]Yoo GH, Lin 1-IS。 lskander AJ, et aL Docelaxel associated pathways in cisplatin resistant head and neck squamous cell carcinoma:a pilot study[J]. Laryngoscope,2005,115(11):1938-1946.
[7]Guerrero D;Guarch R;Ojer A Hypermethylation of the thrombospondin-1 gene is associated with poor prognosis in penile squamous cell carcinoma 2008(06).
[8]Punekar S, Zak S, If,alter VC, et al. Thrombospondin 1 and its mimerle peptide ABT-510 decrease angiogoncsis and inflammation in a routine model of inflammatory bowel disease[J]. Pathobiolngy,2008,75(1):9-21.
[9]Fraipont F.Nicholson AC,Feige JJ,et al. Thrombospondins and tumor angiogenesis Trends [J]. Mol Med,2001,7:401-407.
[10]Damber JE, Vallbo C, A]bertason P, el al. The anti-tumour effect of low-dose continuous chemotherapy may partly be mediated by thrombospoudin[J]. Cancer Chemother Phannacel,2006,58(3):354-360.
[11]Fraipont F.Nicholson AC,Feige JJ,et al. Thrombospondins and tumor angiogenesis Trends Mol Med,2001,7:401-407.
[12]Linda S, Gutierrez. The Role of Thrombospondin 1 on Intestinal Inflammation and Carcinogenesis[J]. Biomark Insights,2008,2008(3):171-178.
[13]Guerrero D, Guarch R, Ojer A, et al. Hypermethylation of the thrombospondin-1 gene is associated with poor prognosis in penile squamous cell carcinoma[J]. BJU Int,2008,102(6):747-755.
[14]Amerongen RV, Bern A. TXR1-mediated thrombospondin repression:a novel mechanism of resistance to taxanes [J].Genes Dev.2006,20:1975-81.
[15]Sparano JA, Wang M, Martino S, et al. Weekly paclitaxel in the adjuvant treatment of breast cancer[J]. N Engl J Med,2008,358(16):1663-1671.
[16]Ferguson T, Wilcken N, Vagg R, et al. Taxanes for adjuvant treatment of early breast cancer [J]. Cochrane Database Syst Rev,2007,(4):CD004421.
[17]Kutuk O, Letai A. Alteration of the mitochondrial apoptotic pathway is key to acquired paclitaxel resistance and can be reversed byABT-737[J]. Cancer Res, 2008,68(19):7985-7994.
[18]Kumar A,Soprano DR,Parekh HK. Cross-resistance to the synthetic Retinoid CD437 in a paclitaxel-resistant human ovarian carcinoma Cell line is independent of the overexpression of retinoic acid Receptor-gamma[J]. Cancer Res.2001 Oct 15;61(20):7552-5.
[19]Hudis C, Dang C. The taxane limbo:how low can we go? [J].Natl Cancer Inst,2008,100(11):761-763.
[20]彭小伟,谭国林.基因芯片技术检测鼻咽癌紫杉醇耐药及耐药逆转相关基因的表达[D].中南大学学报2012,37(1)48-52.
[21]Gillet JP,Efferth T,Steinbach D,et al. Mieroarray-based detection Of multidrug resistance in human tumor cells by expression profiling of ATP-binding cassette transporter genes[J]. Cancer Res.2004Dec15:64(24):8987-93.
[22]Takashi Nakamuraa, Mikio Okaa,1, Kikuo Aizawab.Direct Interaction between a Quinoline Derivative, MS-209, and Multidrug Resistance Protein (MRP) in Human Gastric Cancer Cells[J].Biochemical and Biophysical Research Communications.1995;92:7690.
[23]Johnatty SE, Beesley J, Paul J, et aL ABCB1(MDR I)polymorphisms and progression-free survival among women with ovarian cancer following paclitaxel/ carboplatin chemotherapy[J].Clin Cancer Res,2008,14(17):5594-5601.
[24]Noguchi K, Kawahara H, Kaji A, et aL Substrate · dependent bidirectional modulation of P-glyeoprotein-mediated drug resistance by erlotinib[J].Cancer Sci,2009,100(9):1701-1707.
[25]S Rao, N E Krauss, J M Heerding, C S Swindell, I Ringel, G A Orr and S B Horwitz. Ea al.3'-(p-azidobenzamido)taxol photolabels the N-terminal 31 amino acids of beta-tubulin[J] Journal of Biological,1994;269:3132.
[26]Preisler VK,Wuck D,Stoppe rH,et al.Combination of paclitaxel and radiation:genotoxicity in vitro in four mammalian cell lines[J]. Cancer Lett,1999, 145(1-2):29-33.
[27]Rowinsky EK, Donehower RC. Paclitaxel (taxol)[J]. N Engl J Med,1995, 332(15):1004-1014.
[28]Hutchinson E, A taxing problem [J]. Nat Rev Cancer,2006,6(8):578-579.
[29]Azuma K, Sasada T, Kawahara A, el aL Expression of ERCCI and class Ⅱbeta-tubulin in non-small cell lung cancer patients treated with carboplatin and paclitaxeL Lung Cancer[J].2009,64(3):326-333.
[30]Sere P, Reiman T, Lai R, el aL ClassⅢbeta-tubulin is a marker of paclitaxel resistance in carcinoma of unknown primary site[J].Cancer Chemother Pharmacol, 2007, (6):27-34.
[31]Aoki D, Oda Y, Hattori S, et aL Overexpression of class Ⅲ beta-tubulin predicts good response to taxane-based chemotherapy in ovarian dear cell adenocarcinoma[J].Clin Cancer Res,2009,15(4):1473.1480.
[32]Giannakakou P, SackeA D,L Rang. Y-K,Zhan. Z,Butcrs. J T M,Fojo. T,and Poruchynsky. M.S.Paclitaxel-resistant human ovarian cancer cells have mutant β-tuhulins that exhibit impaired paclitaxel-driven polymerization.[J].Biol. Chem.,272: 17118-17125.1997.
[33]马雪梅,白志刚,张忠涛,等.紫杉醇对乳腺癌细胞紫杉醇耐药基因TXR1表达的影响[J].中国医药生物技术,2010,05(6)：429-433.
[34]马雪梅,白志刚,张忠涛,等.紫杉醇耐药基因TXR1对乳腺癌细胞耐药性的影响[J].中国肿瘤临床,2010,12(6)：1205-1208.
[35]Papadaki C, Mavroudis D, Trypaki M, et al. Tumoral expression of TXR1 and TSP1 predicts overall survival of patients with lung adenocarcinoma treated with first-line docetaxel-gemcitabine regimen[J]. Clin Cancer Res,2009,15(11):3827-3833.
[36]J Souglakos, C Papadaki, et al. Correlation of BRCA1, TXR1 and TSP1 mRNA expression with treatment outcome to docetaxel-based first-line chemotherapy in patients with advanced/metastatic non-small-cell lung cancer[J]. British Journal of Cancer (2011) 104,316-323.
[37]Peng X, Li W, Tan G, et al. Reversal of taxol resistance by cisplatin in nasopharyngeal carcinoma by upregulating thromspondin-1 expression[J]. Anticancer Drugs.2010 Apr;21(4):381-8.
[38]余情杰.TXR1基因在鼻咽癌紫杉醇耐药细胞系中的表达[D].中南大学,2012,5(7)：15-48.
[39]Zhi-Gang BAI,XIANG QU,WEI HAN,XUE-MEI MA and ZHONG-TAO ZHANG, et al. Expression of taxol resistance gene 1 correlates with gastric cancer patient clinical outcome and induces taxol resistance[J].Molecular Medicine REPORTS 2010,3:1071-1078.
[40]姚晓峰.TXR1和TSP1在头颈部鳞癌中表达与紫杉醇耐药相关性的研究[J].2011国际暨全国头颈肿瘤学术大会论文集目录,中国,杭州,342-348.
[41]孙高英,王小元,张晓金.N-乙酰半胱氨酸对子宫颈癌细胞紫杉醇耐药性的影响[J].山东大学学报,2013,3(51)：42-47.