用户名: 密码: 验证码:
非小细胞肺癌组织P53、c-erbB2、MRP蛋白表达及其意义
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
目的:
     探讨癌组织P53、c-erbB2、MRP蛋白表达和非小细胞肺癌(NSCLC)临床病理特征的关系及其预后评估意义。
     方法:
     应用免疫组织化学方法检测NSCLC切除标本P53、c-erbB2、MRP蛋白表达,并与临床病理参数进行比较分析。
     结果:
     NSCLC组织P53、c-erbB2、MRP蛋白表达阳性率分别为53.9%(82/152)、44.1%(67/152)及43.4%(66/152)。P53表达与性别、细胞分化程度、临床分期、淋巴结转移有显著关系,而c-erbB2与各因素间无统计学差异,肺腺癌MRP蛋白表达阳性率(67.6%)明显高于肺鳞癌(33.0%)有统计学差异(P<0.05)。癌组织P53、c-erbB2、MRP联合表达阳性者预后不良:三种蛋白表达均阳性者的1、2、3年生存率明显低于均阴性者(P=0.02、0.01和0.00)。P53、c-erbB2、MRP蛋白表达阳性者单纯手术后生存率明显低于阴性者(P<0.05),P53、c-erbB2、MRP三种蛋白表达均阴性者预后最好,1-2种阳性者次之,3种均阳性者预后最差(P<0.05)。术后辅助化疗组MRP、c-erbB2蛋白表达阳性者的生存率低于阴性者(P<0.05),但P53蛋白表达阳性与阴性患者的生存率无统计学差异(P=0.82);MRP与c-erbB2表达双阴性者生存率显著高于双阳性者,MRP或c-erbB2单一阳性的生存率介于前两者之间(P=0.01)。多因素Cox分析显示细胞分化程度、c-erbB2是影响NSCLC疗效和预后的独立预测因子。
     结论:
     肿瘤组织P53、c-erbB2、MRP三种蛋白同时高表达的NSCLC病例预后较差,术后检测P53、c-erbB2、MRP表达对评估可手术NSCLC疗效和预后有一定意义。
Aim:
     To investigate prognostic and predictive importance of of P53、c-erbB2、MRP expression and its relationship with clinicopathologic parameters in non-small-cell lung cancer (NSCLC).
     Method:
     Detection of P53、c-erbB2、MRP protein expression in 152 tumor samples from resected primary NSCLCs was performed by immunohistochemical staining using a polyclonal antibody.The correlation of proteins, survival and clinicopathologic parameters was investigated in 152 patients undergoing potentially curative surgery.
     Results:
     The positive rate of P53、c-erbB2、MRP expression was 53.9%(82/152), 44.1%(67/152) and 43.4%(66/152) respectively. There were significantly relationship of P53 positive expression with gender, tumor differntiation, TNM stage and lymph metastasis respectively (P<0.05), but no relationship of c-erbB2 expression with clinicopathologic parameters in NSCLC. MRP positive rate (67.6%) in adenocarcinoma was significantly higher than (33.0%) in squamous-cell carcinomas (P<0.05). Overall survival was significantly correlated with the co-overexpression of P53, c-erbB2 and MRP proteins. Overall survival rate in 1,2,3 years with the co-positive were respectively 72.6%,54.8% and 32.2%, lower than co-negative 92.1%,78.5% and 63.4% (P=0.02,0.01 or 0.00); co-positive lower than co-negative by surgery alone (P<0.05), and that co-positive with c-erbB2 and MRP lower than co-negative by surgery plus chemotherapy(P=0.01). It was showed by Cox's model analysis that c-erbB2 expression or cell differentiation was an independent prognostic factor in patients with completely resected NSCLC.
     Conclutions:
     These findings clearly suggest that the specific oncoprotein co-overexpression is correlated with NSCLC patients' overall survival. Detection of P53, c-erbB2 and MRP co-expression may be a useful predictive indicator of prognosis. C-erbB2 expression is an independent prognostic factor, and may provide a useful predictive indicator of response to chemotherapy or molecular targeted therapies with c-erbB2 inhibitors in NSCLC.
引文
[1]Arriagada R, Bergman B, Dunant A, et al:Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer [J]. N Engl J Med,2004,350(4):351-360.
    [2]Mountain CF. Revisions in the International System for Staging Lung Cancer. Chest[J],1997, 111(6):1710-1717.
    [3]强欣.乳腺癌组织中C-erbB-2、P53、ER、PR的表达与预后因素的关系[J].内蒙古民族大学学报,2008,23(4):423.
    [4]王延明,王文杰,王爱民,等.P53表达与肺癌多药耐药的相关性研究[J].肿瘤研究与临床,2002,14(1):18-20.
    [5]Harada T, Ogura S, Yamazaki K, et al. Predictive value of expression of P53, bcl-2 and lung resistance-related protein for response to chemotherapy in non-small cell lung cancers[J]. Cancer Sci,2003; 94 (4):394-399.
    [6]王同,梅晓冬,徐晓玲,等.利福霉素逆转多药耐药细胞系A549/ADM的实验研究[J].蚌埠医学院学报,2007,32(6):640-642.
    [7]Benlloch M, Ortega A, Ferrer P, et al. Acceleration of glutathione efflux and inhibition of gamma-glutamyltranspeptidase sensitize metastatic B16 melanoma cells to endothelium-induced cytotoxicity [J]. Journal of Biological Chemistry, 2005,22 (5):6950.
    [8]Lian J, Li L, Sun RF. Correlation of Ki67、C-erbB-2 and VEGF expression in breast cancer and their clinical significance [J]. Shanxi Med Univ,2009,40(2): 125-127.
    [9]Hayes DF, Thor AD. C-erbB2 in breast cancer:development of a clinically useful marker [J]. Semin Oncol,2002,29 (3):231-245.
    [10]Serrano Olvera A, Duenas Gonzalez A. Gallardo Rincon Prognostic, predictive and therapeutic implications of HER2 in invasive epithelial ovarian cancer [J]. Cancer Treat Rev,2006,32 (3):180-190.
    [11]Valerie R, David K, Ennapadam V, et al. Aberrant P53 expression predicts clinical resistance to cisplatin-based chemotherapy in locally advanced non-small cell lung cancer [J]. Cancer Res,1995,55(21):5038-5042.
    [12]Izquierdo MA, Shoemaker RH, Flens MJ, et al. Overlapping phenotypes of multidrug resistance among panels of human cancer cell lines [J]. Int J Cancer, 1996,65(2):230-270.
    [13]步宏,庞宗国.C-erbB-2基因在乳腺癌中的研究进展[J].基因快讯,2001,1(1):12.
    [14]Linzer DI, Levine AJ. Characterization of a 54K Dalton cellular SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells [J]. Cell,1979,17(1):43.
    [15]Helton ES, Chen X. r63 modulation of the DNA damage response [J]. J Cell Biochem,2007,100 (4):883-896.
    [16]Stiewe T. The P53 family in differentiation and tumorigenesis [J]. Nat Rev Cancer,2007,7 (3):165-168.
    [17]Laptenko O, Prives C. Transcriptional regulation by P53:one protein, many possibilities [J]. Cell Death difer,2006,13(6):951-961.
    [18]Hodge DR, Peng B, Cherry JC, et al. Interleukin 6 supports the maintenance of P53 tumor suppressor gene promoter methylatiqn [J]. Cancer Res,2005,65 (11): 4673.
    [19]Kristy Boggs, David Reisman. C/EBP beta participates in regulating transcription of the P53 gene in response to mitogen stimulation [J]. J Biol Chem,2007,282 (11):7982.
    [20]Chen J, Chang C. P53 isoform D113P53 is a P53 target gene that antagonizes P53 apoptotic activity via Bc12xL activation in zebrafish [J]. Genes Development, 2009,23 (3):278-290.
    [21]Flores ER, Tsai KY, Crowley D, et al. p63 and p73 are required-dependent apoptosis to DNA damaged [J]. Nature,2002,416(6880):560-564.
    [22]Marchetti A, Buttitta F, Merlo G, et al. P53 alterations in non-small cell lung cancers correlate with metastatic involvement of hilar and mediastinal lymph nodes [J]. Cancer Res,1997,53:2845-51.
    [23]Tsao MS, Sarit AR, Keyue D, et al:Prognostic and Predictive Importance of P53 and RAS for Adjuvant Chemotherapy in Non-Small-Cell Lung Cancer[J].J Clin Oncol,2007,25(33):5240-5247.
    [24]姜斌,龚圣济,姚宝娣,等FHIT和P53基因在非小细胞肺癌中的表达[J].上海第二医科大学学报,2005,25(11):1136-1137.
    [25]白皓,张雪艳,纪灏,等:P53和nm23在非小细胞肺癌中的表达及其临床意义[J].实用肿瘤杂志,2004,19(6):497-500.
    [26]李爱武,易祥华,周彩存,等P53、c-erbB2和nm23基因表达在非小细胞肺癌中的临床意义[J].临床肿瘤学杂志,2005,10(4):346-350.
    [27]柯立,徐美青,魏大中,等.非小细胞肺癌中S100A2和P53蛋白的表达[J].安徽医科大学学报,2010,45(4):558-561.
    [28]顾岩,孙勤暖,付秀华,等.突变型P53、MDM2、caspase-3在非小细胞肺癌的表达及意义[J].内蒙古医学院学报,2009,31(1):29-35.
    [29]Miyatake K, Gemba K, Ueoka H, et al. Prognostic significance of mutant P53 protein, P-glycoprotein and glutathione S-transferase-pi in patients with unresectable non-small cell lung cancer [J]. Anticancer Res,2003; 23(3):2829-2836.
    [30]吴海鹰,谢勉,候景辉,等.Ⅲ期非小细胞肺癌LRP、P53蛋白表达与新辅助化疗疗效及预后的研究[J].肿瘤,2005;25(6):609-612.
    [31]Sengupta S, Harris CC. P53:Traffic cop at the crossroads of DNA repair and recombination [J]. Nat Rev Mol Cell Biol,2005,6(1):44-55.
    [32]黄培钰,梁小曼,林素瑕,等.晚期非小细胞肺癌组织中ERCC1、 Metallothionein、P53表达与铂类耐药性及预后的相关性分析[J].癌症, 2004,23(7):845-850.
    [33]张洪涛.P53与化疗敏感性[J].国外医学:肿瘤学分册,2001,28(5):344-347.
    [34]Lee JS, Yoon A, Kalapurakal SK, et al. Expression of P53 oncoprotein in non-small-cell lung cancer:a favorable prognostic factor [J].J Clin Oncol,1995, 13(8):1893-1903.
    [35]Kwiatkowski DJ, Harpole DH, Godleski J, et al. Molecular pathologic substaging in 244 stage I non-small-cell lung cancer patients:clinical implications [J]. J Clin Oncol,1998,16(7):2468-2477.
    [36]Ebina SM, Mulshine JL, Linnoila RI, et al. Relationship of P53 overexpression and up-regulation of proliferating cell nuclear antigen with the clinical course of non-small-cell lung cancer[J].Cancer Res,1994,54(9):2496-2503.
    [37]Lee E, Lim SJ. The association of increased lung resistance protein exp ression with acquired etoposide resistance in human H460 lung cancer cell lines [J]. Arch Pharm Res,2006,29(11):1018-1023.
    [38]Groot DJ, van der DeenM, Le TK, et al. Indomethacin induces apoptosis via a MRP 1-dependent mechanism in doxorubicin-resistant small-cell lung cancer cells overexpressing MRP1 [J]. Br J Cancer,2007,97 (8):1077-1083.
    [39]Bouhamyia L, Chantot-Bastaraud S, Zaidi S, et al. Immunolocalization and cell expression of lung resistance-related protein in normal and tumoral human resp iratory cells [J]. J Histochem Cytochem,2007,55 (8):773-782.
    [40]Oguri T, Achiwa H, Sato S, et al. The determinants of sensitivity and acquired resistance to gemcitabine differ in non-small cell lung cancer:a role of ABCC5 in gemcitabine sensitivity [J]. Mol Cancer Ther,2006,5(7):1800-1806.
    [41]Kang HK, Lee E, Pyo H, et al. Cyclooxygenase-independent down regulation of multidrug resistance-associated protein21 expression by celecoxib in human lung cancer cells [J]. Mol Cancer Ther,2005,4(9):1358-1363.
    [42]刘东华,章霞芝,陈兴无,等survivin、MDR21. MRP在非小细胞肺癌中的表达 及意义[J].实用肿瘤杂志,2008,23(2):126-130.
    [43]Singhal SS, Singhal J, Nair MP, et al. Doxorubicin transport by RALBP1 and ABCG2 in lung and breast cancer [J]. Int J Oncol,2007,30 (3):717-725.
    [44]Leslie EM, Ito K, Upadhyaya P, et al. Transport of the beta-O-glucuronide conjugate of the tobacco-specific carcinogen 4-(me-thylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) by the multidrug resistance protein 1 (MRP1). Requirement for glutathione or a non-sul-fur-containing analog J Biol Chem, 2001,276 (30):27846.
    [45]Young L C, Camp ling B G, Cole S P, et al. Multidrug resistance proteins MRP3, MRP1, and MRP2 in lung cancer:correlation of protein levels with drug response and messenger RNA levels. Clin Cancer Res,2001,7(6):1798-1804.
    [46]史鹏,刘晶,赵凤芹,等.非小细胞肺癌多药耐药因子的表达相关性及临床意义[J].吉林大学学报(医学版),2007,33(1):151.
    [47]Filipits M, Haddad V, Schmid K, et al. Multidrug resistance proteins do not predict benefit of adjuvant chemotherapy in patients with completely resected non-small cell lung cancer:International Adjuvant Lung Cancer Trial Biologic Program[J]. Clin Cancer Res.2007,13 (13):3892.
    [48]孙征,瞿彩平.MRP在非小细胞肺癌组织中的表达及其临床意义[J].实用临床医药杂志,2009,13(1):70-73.
    [49]Wright SR, Boag AH, Valdimarsson, et al. Immunohistochemical detection of multidrug resistance protein in human lung cancer and normal lung [J]. Clin Cancer Res,1998,4 (9):2279-2289.
    [50]BergerW, Setinek U, Hollaus P, et al. Multidrug resistance markers P-glycop rotein, multidrug protein 1, and lung resistence protein in non-small cell lung cancer:prognostic implications [J]. J Cancer Res Clin Oncol,2005,131 (6): 355-363.
    [51]Brock I, Hipfner DR, Nielsen BS, et al. Sequential coexpression of the multidrug resistance genes MRP and mdrl and their products in VP-16 (etoposide)-selected H69 small cell lung cancer cells [J]. Cancer Res,1995,55 (3):459-462.
    [52]王延明,王爱民,张文杰,等.耐多药相关蛋白基因表达与肺癌病理特征关系的研究[J].中华结核与呼吸杂志,1999,22(9):545-547.
    [53]Ota E,Abe Y,Oshika Y,et al. Expression of the multidrug resistance-associated protein (MRP) gene in non-small-cell lung cancer [J].Br J Cancer,1995, 72(3):550-554.
    [54]Filipits M, Haddad V, Schmid K,et al:Multidrug resistance proteins do not predict benefit of adjuvant chemotherapy in patients with completely resected non-small cell lung cancer:International Adjuvant Lung Cancer Trial Biologic Program[J]. Clin Cancer Res,2007,13(13):3892-3898.
    [55]彭向红,冯奉仪,张伟,等.耐多药相关蛋白在入非小细胞肺癌组织中的表达[J].中华结核与呼吸杂志,1999,22(11):655-658.
    [56]詹茂程,刘叙仪,李吉友,等.多药耐药相关蛋白基因在非小细胞肺癌表达的临床意义[J].中华肿瘤杂志,1999,21(2):112-113.
    [57]Ling YH, Jiang JD, Holland JF, et al. Arsenic trioxide produces polymerization of microtubules and mitotic arrest before apoptosis in human tumor cell lines [J]. Mol Pharmacol,2002,62(3):529.
    [58]Schechter AL, Stern DF, Vaidyanathan L, et al. The neuoncogene:an erb-B2 related gene encoding a 185,0002Mr tumour antigen [J]. Nature,1984,312 (5994):513-516.
    [59]Kristiansen G, Yu Y, Petersen S,et al:Overexpression of c-erbB2 protein correlates with disease-stage and chromosomal gain at the c-erbB2 locus in non-small cell lung cancer[J]. Eur J Cancer,2001,37(9):1089-1095.
    [60]Turken O, Kunter E, Cermik H, et al:Prevalence and prognostic value of c-erbB2 expression in non-small cell lung cancer [J]. Neoplasma 2003,50(3):257-261.
    [61]刘汉勇,王晓玫,单军,等E-cadherin和C-erbB2在非小细胞肺癌中的表达 及其临床病理意义[J].中国误诊学杂志,2008,8(13):3025-3028.
    [62]Kawasaki M, Nakanishi Y, Kuwano K, et al. The utility of P53 immunostaining of transbronchial biopsy specimens of lung cancer:P53 overexpression predicts poor prognosis and chemoresistance in advanced non-small cell lung cancer [J]. Clin Cancer Res,1997,3(7):1195.
    [63]Rosell R, Gonzalez JL, Alberola V, et al. Single-agent paclitaxel by 3-hour infusion in the treatment of non-small cell lung cancer:links between P53 and K-ras gene status and chemosensitivity [J]. Semin Oncol,1995,22(6):12.
    [64]Chin KV, Ueda K, Pastan I, et al. Modulation of activity of the promoter of the human MDR1 gene by Ras and P53 [J].Science,1992,255:459-462.
    [65]Wang Q, Beck WT. Transcriptional suppression of multidrug resistance-associated protein (MRP) gene expression by wild-type P53 [J]. Cancer Res, 1998,58:5762-5769.
    [66]Sullivan GF, Yang JM, Vasisil A, et al. Regulation of expression of the multidrug resistance protein MRP1 by P53 in human prostate cancer cells [J]. J Clin Invest, 2000,105:1261-1267.
    [67]Bahr O, Wick W, Weller M. Modulation of MDR/MRP by wild-type and mutant P53 [J]. J Clin Invest,2001,107:643-646.
    [68]姬明丽,千智斌,徐自超.P53蛋白与非小细胞肺癌多药耐药性的关系[J].新乡医学院学报,2008,25(1):13-15.
    [69]杨廷桐,李秀杰,武俊芳,等.端粒酶反转录酶活化与P53金属蛋白酶29表达对非小细胞肺癌发生的影响[J].新乡医学院学报,2007,24(5):443-447.
    [70]王春福,刘翼军.肺癌细胞的多药耐药性与P53. c2myc. nm23 H1异常表达关系的探讨[J].实用临床医学,2004,5(3):22-24.
    [71]Torre EA, Salimbeni V, Fulco RA. The erbB-2 oncogene and chemotherapy:a mini review [J]. J Chemother,1997,9:51-55.
    [1]Yan F, Jiang Y, Li YM, et al. Reversal of P-Glycoprotein and Multidrug Resistance-Associated Proteinl Mediated Multidrug Resistance in Cancer Cells by HZ08 Isomers, Tetrataisohydroquinolin Derivatives[J]. Biol Pharm Bull,2008,31(6):1258-1264.
    [2]Teodori E, Dei S, Martelli C, et al. The functions and structure of ABC transporters:implications for the design of new inhibitors of P-gp and MRP1 to control multidrug resistance (MDR) [J]. Curr Drug Targets,2006,7(7): 893-909.
    [3]Buda G, Orciuolo E, Maggini V, et al. MDR1 modulates apop tosis in CD34+ leukemic cells [J]. Ann Hematol,2008,87 (12):1017-1018.
    [4]Marquardt D, Center MS. Involvement of vacuolar H (+)-a-denosine triphosphatase activity in multidrug resistance in HL60 cells [J]. J Natl Cancer Inst,1991,83:1098-1102.
    [5]李续建,王椿,乔振华,等.急性髓性白血病细胞MRP基因表达[J].中华肿瘤杂志,1998,20(1):9-11.
    [6]Kawabata S, Oka M, Shiozawa K, et al. Breast cancer resistance protein directly confers SN-38 resistance of lung cancer cells [J]. Biochem Biophys Res Commun,2001,280:1216-1223.
    [7]Sandri MI,Hochhauser D, Ayton P, et al. Differential expression of the topoisomerase Ⅱ α and β genes in human breast cancers[J]. Br J Cancer, 1996,73:1518-1524.
    [8]Scheffer GL, wijngaard PL, Flens MJ, et al. The drug resistance-related protein (LRP) is the human major vault protein [J].Nat Med,1995,1:578-582.
    [9]Litman T, Brangi M, Hudson E, et al. The multidrug-resistant phenotype associated with overexpression of the new ABC half-transporter, MXR(ABCG2)[J].J Cell Sci,2000,113(Pt11):2011.
    [10]Russo D, Marie JP, Zhou DC, et al. Co-expression of anionic glutathione S-transferase (GST Pi) and multidrug resistance [MDR1] genes in acute myeloid and lymphoid leukemias [J]. Leukemia,1994,8:881-884.
    [11]Chin KV, Ueda K, Pastan I, et al. Modulation of the activity of the promoter of the human MDR-1 gene by Ras and P53 [J]. Science,1992,255:459-462.
    [12]Gruss HJ, Dower SK. Tumor necrosis factor ligand superfamily involvement in the pathology of malignant lymphomas [J]. Blood,1995,85:3378-3404.
    [13]Kim WJ, Kakehi Y, Yoshida O. Multi-factorial involvement of multidrug resistance associated [correction of resistance] protein, DNA topoisomerase Ⅱ and glutat hione/glutat hione-s-transferase in non p-glycoprotein-mediated multidrug resistance in human bladder cancer cells [J]. Int J Urol,1997,4:583-590.
    [14]Coles B, Ketterer B. The role of glutat hione and glutathionet ransferases in chemical carcinogenesis [J]. Cris Rev Biochem Mol Biol,1990,25:47-70.
    [15]Brugger D, Brischwein K, Liu C, et al. Induction of drug resistance and protein kinase C genes in A2780 ovarian cancer cells after incubation with antineop lastic agents at sublethal concentrations[J]. Anticancer Res, 2002,22 (6C):4229-4232.
    [16]Bond TD, Valverde MA, Higgins CF. Protein kinase C phosphorylation disengages human and mouse-lap-glycoproteins from influencing the rate of activation of swelling-acitivated chloride currents [J]. J Physiol,1998, 508:333-340.
    [17]Chou CY, Shen MR, Hsu KS, et al. Involvement of PKC-α in regulatory volume decrease responses and activation of volume-sensitive chloride channels in human cervical cancer HT-3 cells [J]. J Physiol,1998,512:435-448.
    [18]郭天剑,袁亚维,孙爱民,等.对MDR肿瘤细胞KBV200的PKC-α亚型cDNA克隆序列的研究[J].肿瘤研究与临床,2002,14:294-297.
    [19]Olejniczak SH, Hernandez-Ilizaliturri FJ. Acquired resistance to rituximab is associated with chemotherapy resistance resulting from decreased Bax and Bak expression[J].Clin Cancer Res,2008 Mar 1,14(5):1550.
    [20]Kullak-Ublick GA, Beuers U, Paumgartner G. Hepatobiliary transport [J]. J Hepatol,2000,32 (Suppl 1):3-18.
    [21]Ferreira C G, Tolis C, Giaccone G. P53 and chemosensitivity [J]. Ann Oncol, 1999,10(9):1011-1021.
    [22]Nachmias B, Ashhab Y, Bucholtz V, et al. Caspase-mediated cleavage converts Livin from an antiapoptotic to a proapoptotic factor:implications for drug-resistant melanoma[J]. Cancer res,2003,63(19):6340.
    [23]Hu Y, Cherton-Horvat G, Dragowska V, et al. Antisense oligonucleotides targeting XIAP induce apoptosis and enhance chemotherapeutic activity against human lung cancer cells in vitro and in vivo [J].Clin Cancer Res, 2003,9 (7):2826.
    [24]Murielle M, Surinder KB. Functions of tumorigenic and migrating cancer progenitor cells in cancer progression and metastasis and their therapeutic implications [J]. Cancer and Metastasis Reviews,2007,26 (1):203-215.
    [25]立彦.P-gp介导的肿瘤多药耐药逆转研究进展[J].放射免疫学杂志,2005,18(2):133-135.
    [26]Rubin EH, Alwis DP, Pouliquen I, et al. A phase I trial of apotent P-glycoprotein inhibitor, Zosuquidar.3HC1 trihydrochloride(LY335979), administered orally in combination with doxorubicin in patients with advanced malignancies [J]. Clin Cancer Res,2002,8(12):3710-3717.
    [27]黄明主,李杰.基因技术在逆转肿瘤多药耐药性上的应用[J].肿瘤,2004,24(6):608-610.
    [28]Poirson BF, Concalves RA, Miceoli L, et al. The expression of drug resistance gene products during the progression of human prostate cancer [J]. Clin Cancer Res,2000,6 (2):643-653.
    [29]关松磊.关于卵巢癌的蛋白质组学和姜黄素的体外抑制研究[D].吉林:吉林大学药学院,2007.
    [30]徐峰,蔡卓夫.肿瘤耐药逆转剂研究进展[J].中南药学,2004,2(5):301-303.
    [31]Kostenko EV, Laktionov PP, Vlassov VV, et al. Downregulation of PGY1/MDR1 mRNA level in human KB cells by antisense oligonucleotide conjugates:RNA accessibility in vitro and intracellular antisense activity [J]. Biochim Biophys Acta,2002,1576 (1-2):143-147.
    [32]Lim MN, Lau NS, Chang KM, et al. Modulating multidrug resistance gene in leukaemia cells by short interfering RNA [J]. Singapore Med J,2007 48(10):932-934.
    [33]李敏,于利利,蔡俐琼,等.Bcl-2反义寡核苷酸逆转人卵巢上皮性癌细胞耐药的体外研究[J].中华妇产科杂志,2006,41(2):121-125.
    [34]Matsuo H, WakasugiM, Takanaga H, et al. Possibility of the reversal ofmultidrug resistance and the avoidance of side effects by liposomesmodified with MRK-16, amonoclonal antibody to P-glycoprotein[J]. J Control Release,2001,77 (1-2):77-86.

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700