Reversal Of Cisplatin-resistance In Human Ovarian Cancer Xenograft Model By MicroRNA-16in Nude Mice

Objective To investigate the effects of microRNA-16in reversing cisplatin-resistance in a mouse xenograft model for human ovarian cancer and to explore the mechanism underlying the effects.Methods Two different mouse xenograft models were generated by transplanting SKOV(3) or SKOV(3)/DDP-resistant ovarian cancer cells into BALB/C nude mice. Single drug treatment, cisplatin alone, was tested in both models. Further, combinations of cisplatin and miR-16Agomir (Cholesterol-conjugated miR-16mimics) or miR-16negative control were tested and compared in DDP-resistant ovarian cancer model. Tumors were removed35days after vaccination and changes of tumor volume were measured. The mRNA level of Bcl-2in tumors was determined by RT-PCR and the expression level of Bcl-2protein was detected by IHC. Statistical analysis was performed using SPSS Versionl8.0for Windows. LSD test was used to analyze the enumeration data. Repeated measures analysis of variance was used to compare the volume of the transplanted tumors in different groups, and the significant size of test of this study was validated as value of0.05.Results There was a larger growth inhibitory rate in cisplatin and miR-16Agomir combination treatment group, and Bcl-2mRNA in this group was lower compared to other groups (P<0.05). Accordingly, Bcl-2protein level was also lower than other groups (P<0.05).Conclusion MicroRNA-16could reverse cisplatin resistance in nude mice model for human ovarian carcinoma by repressing Bcl-2.