AIM:To study the relationship between hypoxia or epidermalgrowth factor (EGF) and the overexpression of vascularendothelial growth factor (VEGF) in hepatocellular carcinoma(HCC) and the signal transduction pathway of the transcriptionof VEGF in hepatoma cells.METHODS:Cobalt chloride and recombinant human EGFwere used to stimulate the hepatoma cell lines HepG_2.VEGFmRNA was detected by using of semi-quantitativepolymerase chain reaction (RT-PCR).Specific inhibitors ofphosphatidylinositol 3-kinase (PI3K) and p42/p44 mitogenactivated protein kinase (MAPK) were used to observe theeffects of the two kinases on the regulation of thetranscription of VEGF in hepatoma cells.RESULTS:The expression of VEGF mRNA in HepG_2 cellscultured in serum-free medium was 0.117.However,100 μmol/L cobalt chloride for 24 h increased theexpression of VEGF mRNA and VEGF mRNA increasedgradually with the increase of the concentration and durationof cobalt chloride.Also,25 ng/mL recombinant human EGFstimulated the expression of VEGF in HepG_2 cells and theexpression increased with the increase of EGF concentration.5 μmol/L LY294002 inhibited the expression of VEGFstimulated by cobalt chloride or recombinant human EGFand the inhibition decreased step by step with increase ofthe concentration of LY294002.But even 20 μmol/L LY294002could not completely block the expression of VEGF.Incontrast,PD98059 had no inhibitory effects on thetranscription of VEGF stimulated by cobalt chloride orrecombinant human EGF,CONCLUSION:The overexpression of VEGF in HCC couldbe promoted by hypoxia and EGF expression in HCC.Thesignal transduction pathway of VEGF transcription in HepG_2cells may be through PI3K pathway,but not through p42/p44MAPK pathway. AIM: To study the relationship between hypoxia or epidermalgrowth factor (EGF) and the overexpression of vascularendothelial growth factor (VEGF) in hepatocellular carcinoma (HCC) and the signal transduction pathway of the transcription of VEGF in hepatoma cells. METHODS: Cobalt chloride and recombinant human EGFwere used to stimulate the hepatoma cell lines HepG_2.VEGF mRNA was detected by using a semi-quantitative polymerase chain reaction (RT-PCR). Specific inhibitors of phosphatidylinositol 3-kinase (PI3K) and p42 / p44 mitogen activated protein kinase (MAPK) were used to observe the effects of the two kinases on the regulation of the transcription of VEGF in hepatoma cells .RESULTS: The expression of VEGF mRNA in HepG_2 cells culture in serum-free medium was 0.117.However, 100 μmol / L cobalt chloride for 24 h increased the expression of VEGF mRNA and VEGF mRNA increasedgradually with the increase of the concentration and durationof cobalt chloride. Also, 25 ng / mL recombinant human EGFstimulated the expression of VEGF in HepG_2 cells and theexpression increased with the increase of EGF concentration.5 μmol / L LY294002 inhibited the expression of VEGFstimulated by cobalt chloride or recombinant human EGFand the inhibition decreased step by step with increase of the concentration of LY294002.But even 20 μmol / L LY294002could not completely block the expression of VEGF. CONTRAST, PD98059 had no inhibitory effects on the transfer of VEGF stimulated by cobalt chloride orrecombinant human EGF, CONCLUSION: The overexpression of VEGF in HCC couldbe promoted by hypoxia and EGF expression in HCC.Thesignal transduction pathway of VEGF transcription in HepG2 cells may be through PI3K pathway, but not through p42 / p44 MAPK pathway.