Role of autophagy in response of epithelial ovarian cancer cells to cisplatin treatment and cisplatin resistance

Abstract

Ovarian cancer survival rate is inversely associated with the extent of tumor metastasis. One of the main treatment approaches against ovarian cancer is employment of platinum based therapies, including cisplatin. Majority of ovarian cancer patients develop cisplatin resistance. We aimed to investigate roles for macroautophagy in response of epithelial ovarian cancer cells to cisplatin, including changes in cell motility, as well as in development of cisplatin resistance. Cisplatin treatment induced autophagy in Caov-3 cells in vitro, as well as resulted in increased cell motility. Pharmacologic inhibition of autophagy by wortmannin eliminated the effect of cisplatin on cell motility. We further selected Caov-3 cells with acquired cisplatin resistance and observed elevated baseline expression of autophagy markers in the resistant cells. Our data indicate a role for autophagy in development of cisplatin resistance by the EOC cells, as well as a potential role for cisplatin-induced autophagy in ovarian tumor metastasis.