ZYX knockdown alleviates chemotherapy resistance in epithelial ovarian cancer

The high mortality of epithelial ovarian cancer (EOC) is largely attributable to chemotherapy resistance. This study identifies Zyxin (ZYX) as a key driver of this resistance. ZYX was overexpressed in chemoresistant EOC patients and corresponding paclitaxel- (A2780/PTX) and cisplatin-resistant (A2780/DDP) cell lines. Functional experiments demonstrated that ZYX knockdown reversed chemoresistance by suppressing proliferation and migration, inducing apoptosis, and causing cell cycle arrest. Mechanistically, ZYX promotes resistance by interacting with Glycogen synthase kinase 3 beta (GSK3B), while its knockdown enhances paclitaxel sensitivity via β-tubulin upregulation and inhibits migration by reducing microfilament formation. Furthermore, ZYX knockdown potentiated paclitaxel efficacy in chemosensitive SKOV3 cells, both in vitro and in vivo. Our findings establish ZYX as a promising therapeutic target for overcoming chemotherapy resistance in EOC.