| Objective: Currently considering hypoxic microenviroment exits in the vast majority of solid tumors, in which HIF(Hypoxia-inducible factor, HIF) was thought to play the central role in tumor cells adapting to hypoxic microenviroment, so the aim of this study is to investigate the radiosensitive effect of hypoxia-inducible factor 1α(HIF-1α) inhibitor YC-1 (3'-(5'-Hydroxymethyl-2'-furyl)-1-benzylindazole) for hypoxic glioma cells and their related mechanism.Methods: Glioma SHG44 and U251 cell lines were cultured in normoxic (20% O2), continuous hypoxia (1% O2) for 12 and 24 h, continuous hypoxia plus YC-1 for 12 and 24 h, respectively. The expression of HIF-1αwas assessed by Western blotting. The radiosensitivity was evaluated by the survival curve, and the sublethal damage repair (SLDR) ability were measured by dose-fraction experiment.Results: The radiosensitivity of SHG44 and U251 glioma cells were lower after hypoxic cultures for 12 and 24h than that of the corresponding cells cultured in normoxic. The OER (oxygen-enhancement ratio) of SHG44 cells in hypoxia for 12 and 24h were 1.22 and 1.37, respectively; The OER of U251 cells in hypoxia for 12 and 24h were 1.44 and 1.23, respectively. The radiosensitivity of SHG44 and U251 cells cultured in hypoxia plus YC-1 for 12 and 24 h were increased significantly compared to the corresponding cells cultured in hypoxia only, the EF (enhancement factor) of YC-1 for SHG44 cells at hypoxia for 12 and 24h was 1.27; and the EF of YC-1 for U251 cells at hypoxia for 12 and 24h was 1.25 and 1.05, respectively. The SLDR were decreased significantly for hypoxic SHG44 and U251 cells which were co-cultured with YC-1.Conclusions: HIF-1αinhibitor YC-1 can increase the radiosensitivity of hypoxic glioma SHG44 and U251 cell lines, and its mechanism is related to SLDR inhibited by YC-1. |
