The Study Of Microenviroment Hypoxia On Glioma Cells Radiosensitivity Through Cancer Stem Cell Pathway And Its Related Mechanism

Objective: To study the effect of microenviroment hypoxia on giloma cells radiosensitivity through cancer stem cells pathway, and to explore the related mechanism.Methods: Glioma cells lines SHG44 and U251 were cultured in normoxia (20﹪O2)or continuous hypoxia(1﹪O2) for 12h and 24h with or without YC-1,an agenet widely used as a potent inhibitor of HIF-1αin vitro and in vivo. The fraction of glioma cells 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 expression of HIF-1αand its downstream gene Notch1(Notch1-ICD).Results: (1)SHG44 and U251 glioma cells cultured in hypoxia for 12h and 24h contained a higher fraction of cells expressing CD133 and had lower radiosensitivity than the corresponding cells cultured in normoxic, and the expression of HIF-1αand Notch1 was enhanced. (2)SHG44 and U251 glioma cells cultured in hypoxia for 12h and 24h with YC-1 contained a low fraction of cells expressing CD133 and had higher radiosensitivity than the cells cultured in hypoxia for corresponding time without YC-1.Conclusion: Microenviroment hypoxia could increase the radioresistance of glioma cells through enrichment of cancer stem cells,HIF-1α-Notch1 signal pathway may play an important role in this process.