Effect Of Sirolimus On The Expression Of HIF-1α And VEGF In Hepatocellular Carcinoma HepG2 Cells In Vitro

Objective To investigate the effect of sirolimus on the expression of hypoxia-inducible factor-1α(HIF-1α) and vascular endothelial growth factor(VEGF) in human hepatocellular carcinoma HepG2 cells induced by cobalt chloride in vitro.Methods Cobalt chloride was used to mimic the cell hypoxic microenvironment,and HepG2 cells were divided into 5 groups according to the different concentration of cobalt chloride,namely Oμmol/L group,50μmol/L group,100μmol/L group,200μmol/L group, and 400μmol/L group;We chosed 200μmol/L of the concentration of cobalt chloride to mimic tumor hypoxic microenvironment,and affiliated with different concentration of sirolimus(0nmol/L,10nmol/L,20 nmol/L,30 nmol/L,40 nmol/L) to treat the cells for 24h.Protein and mRNA levels of HIF-1αand VEGF were detected by immunohistochemistry and semi-quantitative reverse transcription-polymerase chain reaction(RT-PCR),and the contribution of sirolimus in this study was analyzed.Results①With the increasing concentration of cobalt chloride,the levels of mRNA and protein expression of HIF-1αand VEGF was increasing(P＜0.05);②The levels of mRNA and protein expression of HIF-1αand VEGF of HepG2 cells induced by cobalt chloride was degressive with the effect of sirolimus,and it was dose-dependent(P＜0.05).Conclusion The levels of mRNA and protein expression of HIF-1αand VEGF in HepG2 cells can be elevated by the hypoxic microenvironment;HIF-1αand VEGF may play an important role in the cells hypoxic regulation to participate in the tumorous growth.Sirolimus can inhibit the levels of mRNA and protein expression of HIF-1αand VEGF,and it may be one of its antineoplastic mechanisms.