17-DMAG对缺氧肿瘤细胞的辐射敏感性影响

Effects of Radiation Sensitivity of 17-DMAG on Hypoxic Carcinima Cells

目的研究17-DMAG对缺氧模拟剂氯化钴(CoCl_2)诱导的人宫颈癌HeLa细胞的辐射敏感性影响。方法首先应用不同浓度的CoCl_2处理HeLa细胞24h,采用Western blot技术检测HIF-1α蛋白表达量,然后选取浓度为200μmol/L的CoGl_2对Hela细胞进行模拟缺氧处理24 h,应用不同浓度的17-DMAG预处理细胞16h后,接受2、4、6、8Gy不同剂量的射线照射,采用克隆形成实验观察细胞的存活率,应用Western blot技术检测HIF-1α蛋白表达。结果在CoCl_2浓度为200μmol/L时HIF-1a蛋白表达量最强;不同浓度17-DMAG处理组的HeLa细胞在不同照射剂量组间的存活率差异均有高度统计学论(均P<0.01);17-DMAG预处理缺氧HeLa细胞后,HIF-1a蛋白表达随药物浓度增加受到显著抑制。结论 17-DMAG预处理可增加缺氧细胞辐射敏感性,其机制可能是通过抑制HIF-1a蛋白表达而发挥作用。

Objective To investigate the radiosensitivity effect of 17-DMAG on human HeLa cells of cervical cancer,which was induced by Hypoxia mimetic cobalt chloride（CoCl_2）.Methods First, HeLa cells was treated by different concentrations of CoCl_2 for 24 hours.And HIF-1αprotein level was detected by Western blot analysis.Then the HeLa cells was dealed with CoCl2 in concentration of 200μmol/L.Cells were pre-treated with different concentrations of 17-DMAG 16h after receiving different doses of 2,4,6,8 Gy irradiation.The method of colony-forming was used to detect the radiation sensitivity. HIF-la protein level was detected by Western blot analysis.Results When CoCl2 was in concentration in 200μmol/L,the HIF-1a protein expression was highest;HeLa cells were cultured in different concenreations of 17-DMAG and exposed to different doses of Irradiation,the cell servival rate was significant（P〈0.01）;After 17-DMAG pretreatment hypoxia of HeLa cells,HIF-1a protein expression with the drug concentration were inhibited significantly.Conclusions 17-DMAG pretreatment hypoxia of HeLa cells can enhance radiosensitization and the mechanism may be through inhibition of HIF-1a protein expression.