Background and purpose:Although the structure and function between hypoxia inducible factor-2 alpha(HIF-2a) and hypoxia inducible factor-1 alpha(HIF-1a) is very conservative,they can not be replaced by each other in terms of biological role.Under hypoxic condition,they could express differently.We examined the differential expression of hypoxia inducible factor-2 alpha(HIF-2α) and hypoxia inducible factor-1 alpha(HIF-1α) in SMMC-7721 hepatoma cells after prolonged hypoxia,and explore the possible regulatory mechanism.Methods:Using 1% mionectic incubator to simulate the anoxic circumstance of SMMC-7721 hepatoma cells,and measure the expressional quantum of mRNA and protein of HIF-1α,HIF-2α,and mRNA of natural antisense of HIF-1αlpha(aHIF),and at the same time the half life of HIF-1,HIF-2α mRNA by using CoCl_(2) and transcription inhibitor 5,6-dichlorobenzimidazole-1-beta-d-ribo furanoside(DRB).Results:Acute hypoxia induces rapidly the accumulation of HIF1 and HIF-2α protein in hepatoma cells.With prolonged hypoxia,the HIF-1α mRNA decline,whereas HIF-2α and aHIF protein increases.Conclusions:HIF-2α may play an important role in the progress of the hepatoma cells.aHIF may participate in the regulation of HIF-1α mRNA.