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

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.