Effect and mechanism of HIF-1α on human non-Hodgkin lymphoma apoptosis

OBJECTIVE:To investigate the role of HIF-1α expression in control of apoptosis of human non-Hodgkin lymphoma(NHL) cells in normoxic condition,and explore the mechanism mediating this effect.METHODS:Human non-Hodgkin lymphoma cell lines were pre-treated by Echinomycin(EC),a HIF-1α antagonist.Apoptosis levels were determined with Annexin-Ⅴdying method.Expression levels of Survivin and apoptotic related protein Bcl-2 and Caspase-3 were evaluated by Western blot.Antisense plasmid of HIF-1α was transfected in cells followed by Western blot for determination of expression level of Survivin protein.RESULTS:Inhibition of HIF-1α with EC significantly induced apoptosis of human NHL cells in a time and dose dependent manner(P0.05).At the same time,EC significantly reduced the expression level of Survivin as well as the levels of apoptotic related protein Bcl-2 and Caspase-3(P0.05).The effect of down-regulation on Survivin expression was also achieved in NHL cell lines transfected by Antisense plasmid of HIF-1α(P0.05).CONCLUSION:Inhibition of HIF-1α can induce cell apoptosis in human NHL cell in normoxic condition through down-regulation of Survivin expression.