| TONG Liu-mei,FENG Li-bo,LU Xue-guan,et al.Effect of microenviroment hypoxia on glioma cells radiosensitivity through cancer stem cell pathway[J].Chinese Journal of Radiological Medicine and Protection,2010,30(2):165-168 |
| Effect of microenviroment hypoxia on glioma cells radiosensitivity through cancer stem cell pathway |
| Received:August 18, 2009 |
| DOI： |
| KeyWords:Glioma Hypoxia Cancer stem cell HIF-1α Notch 1 |
| FundProject:江苏省自然科学基金面上项目(BK2009126);江苏省高校自然科学基金项目(09KJB320012) |
| Author Name | Affiliation | E-mail | | TONG Liu-mei | Department of Radiation Oncology, Second Affiliated Hospital of Soochow University, Suzhou 215004, China | | | FENG Li-bo | Department of Radiation Oncology, Second Affiliated Hospital of Soochow University, Suzhou 215004, China | | | LU Xue-guan | Department of Radiation Oncology, Second Affiliated Hospital of Soochow University, Suzhou 215004, China | luxueguanok@yahoo.com.cn | | CHEN Lie-song | Department of Radiation Oncology, Second Affiliated Hospital of Soochow University, Suzhou 215004, China | | | GUO Xin-wei | Department of Radiation Oncology, Second Affiliated Hospital of Soochow University, Suzhou 215004, China | | | TIAN Ye | Department of Radiation Oncology, Second Affiliated Hospital of Soochow University, Suzhou 215004, China | |
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| 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 cell lines SHG44 and U251 were cultured in normoxia(20% O2) or continuous hypoxia(1% O2)for 12 and 24 h. 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 expressions of HIF-1α and its downstream gene Notch 1. Results 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, SF2 (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 cell line was decreased in hypoxia. The protein expressions of HIF-1α and Notch1 genes were elevated more significantly for cells cultured in hypoxia for 12 and 24 h than for those in normoxia. Conclusions Microenviroment hypoxia could increase the radioresistance of glioma cells through enrichment of cancer stem cella, and HIF-1α - Notch1 signal pathway may play an important role in this process. |
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