氧化应激向还原应激转变在砷致细胞恶性增殖中的作用

Objective] To investigate the shift from oxidative to reductive stress and its role in arsenic induced malignant proliferation of human skin keratinocytes (HaCaT), and to provide necessary basic information for in-depth study of the mechanism of arsenic carcinogenesis. [ Methods] The changes of KEAP1, NRF2 and G6PD proteins in HaCaT cells treated with 0.0-or 1.0 uM sodium arsenite up to 35generation at each key generation (0, 1, 7, 14, 21, 28, 35) were examined using the Western-Blot method; and NRF2 siRNA was used to treat HaCaT cells stained up to 35 generations. HThe role of the shift from oxidative stress to reductive stress in arsenic-induced malignant cell proliferationaCaT cells were treated The role of the shift from oxidative stress to reductive stress in arsenic-induced malignant cell proliferationwith NRF2-siRNA to 35 generations, and the protein changes of NRF2 and G6PD were detected by Western-Blot, the changes of cellular redox indexes were also detected. [ Results] KEAP1, NRF2 and G6PD protein levels gradually increased during the malignant transformation of arsenic induced cells, with statistically significant differences compared with the control group (P<0.05); In the early stage of arsenic-induced malignant cell proliferation, the cells were in a state of oxidative stress, with significantly elevated levels of hydrogen peroxide and superoxide (P<0.05) With prolonged exposure to the toxicant, there was a gradual transition to a state of reducing stress, with significant decreases in the NADPH/NADP+ and GSH/GSSG ratios (P<0.05) after transfection of T HaCaT cells with NRF2 siRNA, the levels of NRF2 and G6PD proteins were significantly reduced (P<0.05), and reverses the imbalance in cellular redox homeostasis (P<0.05). decreased (P<0.05). [ Conclusion] The results of this experimental study indicate that the shift from oxidative stress to reducing stress during arsenic-induced malignant cell proliferation promotes malignant cell proliferation.