Hydrogen Sulfide Contributes to Hypoxia-induced Radioresistanceon Hepatoma Cells

Growing evidence has demonstrated that,as an endogenous signaling gasotransmitter,hydrogen sulfide (h 2s) plays an important role in regulating numerous biological functions. the role of h 2s in hypoxia-induced radioresistance on hepatoma cells was investigated in the present work. results showed that,when hepg2 cells were maintained in hypoxia circumstances for 4 h,the cellular radioresistance was extensively increased so that the oxygen enhancement ratio of the survival fraction approached 2.68. under this hypoxic condition,when the cells were treated with dl-propargylglycine (ppg) and aminooxyacetic acid (aoaa),a specific inhibitor of h2s synthase of cystathionine-γ-lyase (cse) and cystathionine-β-synthase (cbs) respectively,radiation responses including cell killing,micronuclei (mn) formation,and caspase-3 activity were significantly enhanced. however,treatment of cells with low concentrations of nahs (≤ 100 μm) protected cells from these radiation damages. western bolting assay showed that cse and cbs were over-expressed in the irradiated hypoxic cells in a dose dependent manner. moreover,when the hypoxic hepg2 cells were treated with nahs together with glibenclamide,a specific inhibitor of k +atp channels,the role of exogenous h 2s in radioprotection was partly eliminated. this study demonstrated that h 2s contributed to hypoxia-induced radioresistance probably via the opening of k +atp channels,which suggests that the endogenous h 2s synthase could be a potential radiotherapeutic target for a hypoxic tumor.