Effects of arsenic trioxide on cell proliferation, apoptosis and HIF-1α expression in human liver cancer HepG2 cells cultured under hypoxic conditions

AIM:To investigate the effects of arsenic trioxide(As2O3) on cell proliferation,apoptosis and hypoxia-inducible factor-1α(HIF-1α)expression in human liver cancer HepG2 cells cultured under hypoxic conditions.METHODS:Hypoxia was induced with cobalt chloride(CoCl2).After HepG2 cells were incubated with different concentrations of As2O3(1.0,2.0,4.0 and 8.0 μmol/L) for 12,24 and 48 h under hypoxic conditions,cell proliferation was determined by MTT assay,and cell apoptosis was evaluated by Hoechst staining.HepG2 cells were then divided into three groups:normal control group,hypoxia group,and As2O3 treatment group.After HepG2 cells were incubated with As2O3 at concentrations of 4.0 and 8.0 μmol/L for 48 h under hypoxia,the expression of HIF-1α protein was detected by immunocytochemistry.RESULTS:As2O3 inhibited proliferation but induced apoptosis of HepG2 cells in a doseand time-dependent manner under both normoxic and hypoxic conditions(both P < 0.01).No significant differences were noted in the reduced proliferation rates of cell proliferation(38.40% vs 37.83%,P > 0.05)and apoptosis rates(45.25% vs 49.28%,P > 0.05)between HepG2 cells treated with 8.0 μmol/L As2O3 for 48 h under normoxic and hypoxic conditions.Immunocytochemistry analysis revealed that HIF-1α was weakly expressed in HepG2 cells under normoxia.After hypoxic induction for 48 h,HIF-1α expression was significantly up-regulated(t = 114.37,P < 0.05).The expression of HIF-1α protein gradually decreased with the increase in the concentration of As2O3 under hypoxia(F = 347.042,P < 0.01).CONCLUSION:As2O3 can inhibit proliferation but induce apoptosis of HepG2 cells under hypoxia possibly by down-regulating HIF-1α protein expression.