Oxaliplatin regulates the autophagy of skin squamous cell carcinoma cell line through HMGB1 pathway

Abstract

Purpose: To determine the influence of oxaliplatin on skin squamous cell carcinoma cell line, and the involvement of autophagy- regulating pathway of high mobility group box 1 (HMGB1) in the process. Methods: A431 cells cultured in vitro were used. The cells were  divided into groups A (treated with different concentrations of oxaliplatin) and B (treated with different concentrations of oxaliplatin combined with autophagy inhibitor 5 mmol/l3-ma). Changes in expression levels of autophagy marker molecules LC3-Ⅰ, LC3-Ⅱ, p62 and  HMGB1 in A431 cells treated with different concentrations of oxaliplatin and different concentrations of HMGB1 were evaluated by  Western blotting. Viability of A431 cells in both groups was assessed by CCK-8 assay. Results: With increase in oxaliplatin concentration,  LC3-Ⅱ levels in A431 cells were up-regulated, p62 expression decreased, while autophagy level was increased significantly (p < 0.05). With  increase in HMGB1 protein concentration, LC3-Ⅱ level in A431 cells was raised, while p62 level was reduced, while the level of autophagy  was significantly increased (p < 0.05). Oxaliplatin treatment led to significantly higher expression level of HMGB1 in the experimental  group than in the control group without oxaliplatin treatment. The viability of oxaliplatin-treated group was dose-dependently and significantly lower (p < 0.05) than that of the control group. Compared with the control group, the cell viability of the 3-mA + oxaliplatin  group also showed a downward trend, and the decrease was greater than that of oxaliplatin-treated group (p < 0.05). Conclusion:  Oxaliplatin upregulates autophagy by promoting HMGB1 protein expression, which may be a protective mechanism of tumor cells  against oxaliplatin cytotoxicity thereby making HMGB1 protein a potential target in skin cancer therapy.