| XU Hui-ying,LIU Xiao-dong,DONG Yong-qiang,LI Wen-na,LI Cai-hong,LIU Bing,MA Shu-mei.Effects of hypoxia-inducible factor-1α on radiation-induced autophagic cell death in breast cancer cells[J].Chinese Journal of Radiological Medicine and Protection,2012,32(5):455-459 |
| Effects of hypoxia-inducible factor-1α on radiation-induced autophagic cell death in breast cancer cells |
| Received:February 27, 2012 |
| DOI：10.3760/cma.j.issn.0254-5098.2012.05.002 |
| KeyWords:Autophagy X-rays Hypoxia Hypoxia-inducible factor-1α Radiosensitivity |
| FundProject:国家自然科学基金(30970682;30770649); 国家大学生创新项目(2010A72110) |
| Author Name | Affiliation | E-mail | | XU Hui-ying | Key Laboratory of Radiobiology, Ministry of Health, School of Public Health, Jilin University, Changchun 130021, China | | | LIU Xiao-dong | Key Laboratory of Radiobiology, Ministry of Health, School of Public Health, Jilin University, Changchun 130021, China | | | DONG Yong-qiang | Key Laboratory of Radiobiology, Ministry of Health, School of Public Health, Jilin University, Changchun 130021, China | | | LI Wen-na | Key Laboratory of Radiobiology, Ministry of Health, School of Public Health, Jilin University, Changchun 130021, China | | | LI Cai-hong | Key Laboratory of Radiobiology, Ministry of Health, School of Public Health, Jilin University, Changchun 130021, China | | | LIU Bing | Key Laboratory of Radiobiology, Ministry of Health, School of Public Health, Jilin University, Changchun 130021, China | | | MA Shu-mei | Key Laboratory of Radiobiology, Ministry of Health, School of Public Health, Jilin University, Changchun 130021, China | shmm2001@yahoo.com.cn |
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| Abstract:: |
| Objective To study the effects of hypoxia-inducible factor-1α (HIF-1α) on radiation-induced autophagic cell death in breast cancer cells.Methods MCF-7 cells were divided into four groups: control (normoxia, 21% Oxygen), irradiation (8 Gy X-rays), hypoxia (Cobalt chloride, CoCl2) and irradiation with hypoxia (CoCl2). 150 μmol/L CoCl2 was utilized to induce hypoxic conditions. Western blot was applied to detect the expression of HIF-1α and MAPLC3. MDC and Hoechst staining were used to detect autophagy and apoptosis. Radiosensitivity was detected by cloning formation. The short hairpin interfering RNA (shRNA) retroviral transduction particles targeting HIF-1α was transfected into MCF-7 cells to establish HIF-1α knockdown cells, then the radiosensibility, autophagy and apoptosis were detected. Results Compared with control group and irradiation group, the protein level of HIF-1 increased obviously in the normaxia, irradiation, hypoxia and irradiation with hypoxia groups,and the values were 0,0,1.00,1.89, respectively. The expression levels of MAPLC3 were markedly up-regulated in irradiation, hypoxia and irradiation with hypoxia groups as compared with control,and the ratios of LC3II/LC3I were 1.15, 1.73, 2.38 and 3.60, respectively. The radiosensitivity of MCF-7 cells decreased in the following order: normoxia with 3MA > normoxia > hypoxia with 3MA > hypoxia. HIF-1α knockdown cell (pSUPER-HIF-1α Ri) and vector control were constructed. After treatment with CoC12, survival fraction of MCF-7-pSUPER was significantly higher than that of control(t=3.080, 6.946, 6.658, 6.380, P<0.05), and radiosensitivity was down-regulated after irradiation, but there was no significant difference between normoxia and hypoxia in survival fraction of MCF-7-pSUPER-HIF-1α Ri. After treatment of irradiation or hypoxia, the autophagic fractions in MCF-7-pSUPER-HIF-1α Ri significantly decreased, reduced by 21.1%, 25.5%, 15.5%,respectively(t=4.635, 4.738, 6.354, P<0.05)as compared with MCF-7-pSUPER, but there was no change in apoptosis. Conclusions HIF-1α may increase radiation-induced autophagy and decrease radiosensitivity, but have no influence on apoptosis. |
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