Glutathione Peroxidase 1 Promotes NSCLC Resistance to Cisplatin via ROS-Induced Activation of PI3K/AKT Pathway

PURPOSE: Reactive oxygen species (ROS)-induced cytotoxicity is an important mechanism by which cisplatin kills tumor cells. Glutathione peroxidase family (GPXs) is an important member of antioxidant system which metabolizes intracellular ROS and maintains homeostasis of cells. Altered expressions of GPXs enzymes, especially GPX1, have been described in a variety of human cancers. However, their functional roles in cisplatin-based chemoresistance in human malignancies including non-small cell lung cancer have never been explored. METHODS: B, BCL2, Bax, and phosphorylated AKT were detected with western blot analysis using specific antibodies. RESULTS: B by its chemical inhibitor BAY can significantly downregulate GPX1 expression and restore the cisplatin sensitivity of the cell lines resistant to cisplatin. CONCLUSIONS: B signaling may be an alternative approach for restoring cisplatin sensitivity for NSCLC cells resistant to cisplatin-based chemotherapy.