乙型肝炎病毒X蛋白对肝细胞癌生长因子激活作用的研究

摘要

Objective The expression of insulin-like growth factor Ⅰ receptor(IGF-ⅠR) and the vascular endothelial growth factor(VEGF) in HepG2 cells transfected with a hepatitis B virus X(HBx) expression vector was investigated in an attempt to study their possible relationship to the growth of HBx-induced hepatocellular carcinoma(HCC). Methods The eucaryotic expression vector of HBx gene was constructed and introduced into HepG2 cells. The modified cell HepaG2-X was synchronized in a quiescent state by culture of serum deprivation. The IGF-ⅠR and VEGF were analyzed by immunohistochemical and Western blot technique. Results The positive rate of IGF-ⅠR expression was 84%±3% in the transfected HBx gene cells, 26%±4% in X0 control cells. The positive rate of VEGF expressed x cells was 83%±5%, X0 cells was 28%±6% (P<0.001). The level of IGF-ⅠR and VEGF in serum-starved x modified cells was 1.5 times higher than that of synchronized X0 modified cells. Conclusion Since the IGF-ⅠR is a very important growth factor in sustaining the tumor abnormal growth and the VEGF has a crucial role in inducting tumor angiogenesis, our findings indicate that HBx may play an important role in the processes of HCC by activating IGF-ⅠR and VEGF gene expression.%目的研究乙型肝炎病毒Ｘ（hepatitis B virus，HBx）蛋白对生长因子激活作用，探讨HBx蛋白对肝细胞癌生长的影响。方法构建Ｘ基因真核表达载体，转染入HepG2细胞后，细胞组织化学和免疫印迹法检测胰岛素样生长因子－Ⅰ受体（insulin-like growth factor Ⅰreceptor，IGF-ⅠR）和血管内皮生长因子（vascular endothelial growth factor，VEGF）表达。结果转染HBx基因HepG2细胞（X细胞）IGF-ⅠR表达阳性率为84%±3%，转染空载体对照细胞（X0细胞）为26%±4%；免疫印迹法检测Ｘ细胞有明显条带。VEGF表达Ｘ细胞阳性率为83%±5%，X0细胞为28%±6%，差异有非常显著意义；Ｘ细胞IGF-ⅠR表达增高近1.5倍。结论 HBx蛋白可同时激活IGF-ⅠR和VEGF，在肿瘤恶性生长、转移中起有重要作用。