Increased efficiency of testicular tumor chemotherapy by ultrasound microbubble-mediated targeted transfection of siMDR1.

Abstract

The MDR1 gene encoding P-glycoprotein (P-gp) is an ATP-dependent drug efflux transporter and is related to drug resistance of yolk sac tumors. Drug resistence may be an important factor for the low efficiency of chemotherapy in the treatment of testicular tumors. P-gp, encoded by the MDR1 gene, is an ATP-binding cassette transporter. P-gp exhibits high expression in capillary endothelial cells of the testis and prevents the intracellular accumulation of chemotherapy agents in testicular tumor cells, resulting in drug resistance. In the present study, we aimed to use specific siRNA to silence the expression of the MDR1 gene and P-gp, leading to the reversal of multidrug resistance of testicular tumors and contributing a suitable condition for chemotherapy. Ultrasound microbubble-mediated delivery is a safe and effective tool for gene delivery. In the present study, we demonstrated that ultrasound microbubble-mediated delivery effectively improved the siMDR1 gene transfection in interstitial capillary endothelial cells of the testis, inhibited the expression of P-gp and increased daunorubicin accumulation. The testis tumor model was successfully constructed by injecting 1x10(7) yolk sac tumor cells in 3-week-old Sprague-Dawley rats. Ultrasound microbubble-mediated siMDR1 gene therapy improved the effect of chemotherapy on the testicular tumors. The testicular volume was reduced, the number of tumor cells within the testicular tissues decreased, and pathological changes were mostly recovered. Therefore, the present study indicated that ultrasound microbubble-mediated siMDR1 gene therapy in vivo reversed drug resistance by regulating P-gp expression, providing a promising method for the treatment of testicular tumors.