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Small Interfering RNA Targeting MDR1 Inhibits Ovarian Cancer Growth and Increases Efficacy of Chemotherapy in vivo

Small Interfering RNA Targeting MDR1 Inhibits Ovarian Cancer Growth and Increases Efficacy of Chemotherapy in vivo

作     者:Fu-jun LIU Guo-lan Gao Kai-jia Tu Li-qun Yu Jun Gao 

作者机构:Department of Obstetrics and Gynecology the First Affiliated Hospital Nanchang University Nanchang 330006 China Department of Obstetrics and Gynecology the Second Affiliated Hospital Nanchang University Nanchang 330006 China. 

出 版 物:《Chinese Journal of Cancer Research》 (中国癌症研究(英文版))

年 卷 期:2009年第21卷第4期

页      面:318-324页

核心收录:

学科分类:0710[理学-生物学] 12[管理学] 1201[管理学-管理科学与工程(可授管理学、工学学位)] 07[理学] 08[工学] 071007[理学-遗传学] 

基  金:supported by the grant from the key project of Jiangxi Bureau of Health Science(No.200506) 

主  题:RNA interference siRNA MDR1 gene Ovarian cancer Nude mice 

摘      要:Objective: To further validate a knockdown approach for circumventing the multidrug resistance gene (MDR1), we used small interfering RNA(siRNA) targeting MDR1 gene to inhibit the expression of MDR1 gene and P-glycoprotein(P-gp) in vivo. Methods: Ascite tumor xenografts were established by implanting human ovarian carcinoma cells SKOV3/AR intraperitoneally into the nude mice. The mice were randomized into the following three treatment groups with each group six mice respectively: Taxol, Taxol with lipofectamine and Taxol with siRNA/MDR1- lipofectamine intraperitoneal injection. The tumor growth rate and the ascite growth rate of mice were investigated. The expressions of MDR1 gene and P-gp in mice were determined by reverse transcription-polymerase chain reaction(RT-PCR) and immunohistochemistry respctively. Results: The growth of tumors and ascites in mice treated with Taxol and siRNA/MDR1- lipofectamine was significantly inhibited compared with those in mice of other groups. After 28 days' treatment, the average tumor weight and ascite volume decreased by 43.6% and 29.7% in the group treated with Taxol and siRNA/MDRl-lipofectamine compared with these treated with Taxol alone (P〈0.001). The expressions of MDR1 gene and P-gp in the group treated with Taxol and siRNA/MDRl-lipofectamine were also decreased compared with those in the group treated with Taxol alone (P〈0.001). Conclusion: Small interfering RNA targeting-MDR1 can effectively and specifically suppress the expression of MDRl(P-glycoprotein) and inhibit ovarian cancer growth in vivo.

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