Small interfering RNA targeting MDR1 inhibits ovarian cancer growth and increases efficacy of chemotherapy in vivo

Abstract

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/MDR1-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/MDR1-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 MDR1(P-glycoprotein) and inhibit ovarian cancer growth in vivo.

Highly effective antiangiogenesis via magnetic mesoporous silica-based siRNA vehicle targeting the VEGF gene for orthotopic ovarian cancer therapy

“…RNA interference (RNAi) technology has been intensively evaluated in the treatment of ovarian cancer by knockdown of genes responsible for progression of cancer, which is achieved by delivery vectors. [12][13][14][15][16][17] Two research groups have reported highly effective suppression of ovarian tumor growth by construction of available vectors. One research group synthesized vasohibin-2 (associated with proangiogenic activity) siRNA and mixed it with atelocollagen to inhibit ovarian tumor growth.…”