两种肠癌细胞通过上调NADH提高其顺铂耐药性

isplatin is a first-line chemotherapy agent in the treatment of colorectal cancer. Besides damaging the DNA of cancer cells, Cisplatin can also induce apoptosis of cancer cells by accumulating intracellular reactive oxygen species (ROS). Cisplatin-resistant cancer cell lines reduce the cytotoxicity of cisplatin by scavenging ROS, thus improving the tolerance of cells to cisplatin. But its downstream effectors are still unclear. The ROS, NAD+ and NADH levels of cisplatin-resistant colorectal cancer cells LoVo/DDP and HCT116/DDP were compared in this paper. The results showed that ROS increased with the increase of cisplatin treatment time. The total amount of NAD increased significantly after cisplatin treatment, especially the ratio of NADH/NAD+. When ROS scavengers (N-acetyl-L-cysteine) were administered, ROS decreased and cisplatin resistance increased in colorectal cancer resistant cells, while NADH levels did not increase. According the transcriptome results, it showed that NAD-dependent enzyme were up-regulated generally. NADH was reduced and ROS increased after the use of NAD-dependent enzyme inhibitors on resistant strains, leading to a significant reduction in drug resistance. These results suggest that colorectal cancer cells may produce additional NADH to remove ROS produced by cisplatin, reduce the cytotoxicity of cisplatin, and thus develop resistance to cisplatin.