Hypoxia-induced high mobility group box 1 release in hepatocellular carcinoma cells and its mechanisms

Objective To investigate the effect of hypoxia on extracellular release of high mobility group box 1 (HMGB1) in hepatocellular carcinoma (HCC) cells and its mechanisms.Methods Using hepatocytes QSG-7701 and HCC cells SMMC-7721,the effect of hypoxia (1％ O2,3-24 h) on HMGB1 release,HMGB1 mRNA expression and the intracellular distribution of HMGB1 was observed.Mitogen-activated protein kinase (MAPK) pathway inhibitors were used to explore the mechanisms of hypoxia-induced HMGB1 release.Serum HMGB1 levels in 28 HCC patients were detected.Results Serum HMGB1 levels in HCC patients [(19.3 ±7.2) pμg/L] were significantly higher than those in healthy controls [(4.1 ± 1.6) μg/L,P ＜0.01].HMGB1 concentration in the culture supernatant was narkedly increased at 3 h,and HMGB1 mRNA expression began to increase at 6 h,after QSG-7701 and SMMC-7721 cells were subjected to hypoxia culture.But the changes in SMMC-7721 were more significant than QSG-7701.The intracellular distribution of HMGB1 displayed dramatic translocation and HMGB1 protein in the cytoplasm was increased after SMMC-7721 cells were subjected to hypoxia cuhure for 12 h.SB203580,SP600125 and PD98059 showed partial inhibitory effects on hypoxia-induced HMGB1 release.Conclusion Hypoxia can induce HCC cells to release HMGB1,which mechanisms may involve in MAPK signal transduction pathways. Key words: High mobility group protein B1 protein;  Carcinoma, hepatocellular;  Hypoxia; Mitogen-activated protein kinase signaling system