Abstract 3762: Downregulation of TRPC3 enhances sensitivity to cisplatin and inhibits motility in epithelial ovarian cancer

Abstract

Abstract Epithelial ovarian cancer (EOC) remains the most lethel gynecological malignancy. In the absence of an effective screening strategy, two thirds of patients are diagnosed in advanced clinical stage. Despite chemotherapy with cisplatin and paclitxel, primary or acquired chemoresistance faciltates survival of cancer cells, resulting in disease recurrence and death. Our previous studies indicate that ovarian cancer patients whose tumors overexpress transient receptor potential channel C3 (TRPC3) protein tend to relapse early and have shorter overall survival. In vitro studies indicated that follicle-stimulating hormone (FSH) induced resistance to cisplatin-induced apoptosis could be partially reversed by blocking expression of TRPC3 in EOC cell lines. To enhance sensitivity to platinum compounds, we have investigated the relationship between resistance to cisplatin and TRPC3. We have now found that expression of TRPC3 in recurrent cancer following chemotherapy is higher than in specimens from primary cytoreductive surgery. The expression of TRPC3 in the cisplatin-resistant EOC line A2780cp is higher than in the sensitive parental cell line A2780. An in vitro study showed that transient treatment of the EOC cell line HEY with cisplatin upregulated TRPC3 mRNA and membrane localized protein. Induced cisplatin-resistant cell line HEYcp augmented the expression of TRPC3 and enhanced invasive capacity in cell migration assays. Knockdown of TRPC3 expression in EOC cell lines with specific siRNA or miRNA decreased cell migratory ability and enhanced cisplatin-induced apoptosis when compared to EOC cells treated with scrambled control RNA. Our data indicate that TRPC3 may play an important role in cisplatin-resistance of EOC and could serve as a therapeutic target to resensitize cancer cells to cisplatin in culture and in xenografts. Citation Format: Xiang Tao, Hongyan Jin, Zhenbo Zhang, Robert C. Bast, Youji Feng, Yinhua Yu. Downregulation of TRPC3 enhances sensitivity to cisplatin and inhibits motility in epithelial ovarian cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3762. doi:10.1158/1538-7445.AM2014-3762