高迁移率族蛋白-1在缺氧诱导肝癌细胞侵袭中的作用

The Role of High Mobility Group Box Protein-1 in Hypoxia-induced Hepatocellular Carcinoma Invasiveness

目的探讨高迁移率族蛋白-1(HMGB1)在缺氧诱导的肝癌细胞侵袭中的作用。方法在培养的Hepa1-6肝癌细胞系上,western blot法观察缺氧不同时间后对HMGB1蛋白表达的影响,细胞侵袭小室实验法观察缺氧对细胞侵袭的影响。以抗HMGB1抗体(a-HMGB1)预处理细胞后,观察缺氧对细胞侵袭效应的改变。结果与常氧组比较,缺氧3、6、12、24 h后均可呈时间依赖性促进HMGB1蛋白的表达。缺氧24 h后,Hepa1-6细胞的侵袭能力明显增强。以a-HMGB1中和HMGB1的作用后,细胞的侵袭能力显著降低。结论缺氧可通过诱导HMGB1分子表达而促进肝癌细胞的侵袭能力。

Objective To investigate the role of high mobility group box protein-1（HMGB1） in hypoxia-induced hepatocellular carcinoma invasiveness.Methods Hepa1-6 cells were cultured and hypoxic conditions were attained.The expression level of HMGB1 was detected by western blot and hypoxia-induced cell invasion was evaluated by using invasion chamber.To confirm the role of HMGB1 in cell invasion,anti-HMGB1 neutralizing antibody was used to observe the change in cell invasiveness.Results In cultured Hepa1-6 cells,hypoxia at different time points（3,6,12,24 h） enhanced HMGB1 protein expression in a time-dependent manner.Compared with normal condition,hypoxia significantly promoted cell invasion.Pretreatment with anti-HMGB1 neutralizing antibody largely impaired hypoxia-enhanced cell invasion.Conclusion Hypoxia promotes hepatocellular carcinoma invasiveness via upregulation of HMGB1 expression.