Sodium selenite combined with adriamycin precursor drug promoted the apoptosis of gastric cancer cells SGC-7901 by regulating reactive oxygen species level and mitochondrial function

Objective To investigate the effect of sodium selenite combined with prodrug of adriamycin (PADM) on reactive oxygen species (ROS) level and mitochondrial function of gastric cancer cells SGC-7901 and the apoptotic mechanism. Methods SGC-7901 cells in logarithmic growth stage were taken and divided into the control group, 2.93 μg/ml sodium selenite (Na2SeO3) treatment group, 2 μg/ml PADM treatment group and Na2SeO3 + PADM combined treatment group. After 48 h, ROS and apoptosis levels, the changes of mitochondrial membrane potential in cells, the permeability of mitochondrial membrane and the expression of apoptosis-related proteins were detected. Results As compared with control group, Na2SeO3 group, the ROS levels in PADM group and combined treatment group were significantly increased (all P=0.000). As compared with the control group, the apoptosis rate in Na2SeO3 group, PADM group, and combined treatment group increased significantly (all P=0.000). As compared with the control group, the level of mitochondrial membrane potential depolarization in Na2SeO3 group, PADM group and combined treatment group increased significantly (all P=0.000). As compared with the control group, the mitochondrial permeability transition pore (mPTP) activity level in Na2SeO3 group, PADM group and combined treatment group increased significantly (all P=0.000). In addition, as compared with the control group, the expression levels of cytochrome C (Cyt C), p53, B cell lymphoma/leukemia-2 associated X protein (bax), Cleaved-cysteinyl aspartate-specific protease (Caspase)-9 and Cleaved-Caspase-3 in each drug treatment group were significantly increased, and those of B cell lymphoma/leukemia-2 (bcl-2) protein was significantly decreased. Conclusion Sodium selenite in combination with adriamycin precursor drug PADM can significantly promote the gastric cancer SGC-7901 cells apoptosis, which may be closely related to the enhancement of cell ROS level, the increase of cell mitochondrial membrane potential depolarization level, and the permeability of mitochondrial membrane and then the activation of mitochondrial apoptosis signaling pathway. Key words: Gastric cancer; Sodium selenite; Prodrug of adriamycin; Reactive oxygen species; Mitochondria; Apoptosis