Xanthatin induce DDP‐resistance lung cancer cells apoptosis through regulation of GLUT1 mediated ROS accumulation

Chemoresistance to cisplatin (DDP) therapy is a major obstacle that needs to be overcome in treating lung cancer patients. Xanthatin has been reported to exhibit an antitumor effect on various cancers, but the function of xanthatin in DDP-resistance lung cancer remains unclear. The study aimed to explore the effect and mechanisms of xanthatin on proliferation, apoptosis, and migration in DDP-resistance lung cancer cells. In the present study, xanthatin suppresses the expression of glucose transporter 1 (GLUT1), attenuates the pentose phosphate pathway (PPP), and causes ROS accumulation and apoptosis, thereby mitigating the antioxidative capacity in DDP-resistance cells. Previous studies have shown that GLUT1 is associated with resistance to platinum drugs. We found that GLUT1 was significantly increased in the DDP-resistant lung cancer cell line compared to the parental cell line, and xanthatin significantly downregulated GLUT1 expression in DDP-resistant lung cancer cells. Notably, overexpression of GLUT1 significantly reduced the production of ROS and increased cellular NADPH/NADP+ and GSH/GSSG ratios. Thus, these results suggest that xanthatin induces DDP-resistance lung cancer cells apoptosis through regulation of GLUT1-mediated ROS accumulation. These findings might provide a possible strategy for the clinical treatment of DDP-resistant lung cancer.