Abstract
Epithelial ovarian cancer (EOC) is one of the most common malignant gynecological tumors. Interval cytoreductive surgery and cisplatin-based chemotherapy are the standard treatments. However, acquired resistance to cisplatin presents a major challenge for improving the overall survival and prognosis of patients. Recent evidence indicates that cytoprotective functions of autophagy in cancer cells is a potential mechanism for chemoresistance. The present study aimed to investigate the mechanisms responsible for cisplatin resistance in EOC cell lines. The results revealed that cisplatin activated autophagy, measured by an increase in the expression of LC3-II by western blot analysis, protecting ovarian cancer cells from cisplatin toxicity. The present study also identified Bcl-2-associated athanogene 3 (BAG3) as a novel autophagy regulator that serves a role in cisplatin resistance. Treatment with cisplatin was observed to enhance BAG3 expression in parental and cisplatin-resistant ovarian cancer cell lines, and the downregulation of BAG3 blocked cisplatin-induced autophagy, thereby increasing cisplatin sensitivity in the EOC cell lines. In conclusion, BAG3 attenuates cisplatin resistance by inhibiting autophagy, suggesting that downregulation of BAG3 may be a useful therapeutic strategy to overcome cisplatin resistance by preventing cytoprotective autophagy in EOC.
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