Abstract
Objective To investigate the effect of microenviroment hypoxia on glioma cells radiosensitivity through cancer stem pathway,and to explore the related mechanism.Methods Glioma eell lines SHG44 and U251 were cultured in normoxia (20%0_2) or continuous hypoxia (1%0_2)for 12 and 24 h.The fraction of glioma ceils with positive expression of CD133 was assayed by flow cytometry.The radiosensitivity of glioma cells was determined by clonogenic cell assay.Western blotting was used to investigate the expressions of HIF-la and its downstream gene Notch 1.Resuits The fraction of glioma cells with positive expression of CD133 was higher after hypoxic culture for 12 and 24 h than that of the corresponding cells cultured in normoxia.Compared to the cells cultured in normoxia,SF_2(survival fraction at 2 Gy)were enhanced significantly in SHG44 and U251 cells cultured in hypoxia for 12 and 24 h.The OER (oxygen-enhancement ratio) of SHG44 cells in hypoxia for 12 and 24 h was 1.54 and 1.38,respectively.The OER of U251 cells was 1.44 and 1.23.respectively.The radiosensitivity of these two eell line was decreased in hypoxia.The protein expressions of HIF-la and Notchl genes were elevated more significantly for cells cultured in hypoxia for 12 and 24 h than for those in normoxia.Conclusions Mieroenviroment hypoxia could increase the radioresistance of glioma cells through enrichment of cancer stem cella.and HIF-la-Notchl signal pathway may play an important role in this process. Key words: Glioma; Hypoxia; Cancer stem cell; HIF-1α; Notch 1
Published Version
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