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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.
Objective: To 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. 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’ trea tment, 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 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.