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目的探讨乏氧诱导因子1α(HIF-1α)抑制剂YC-1对乏氧脑胶质瘤SHG44细胞株的放射增敏作用及其作用机制。方法选择脑胶质瘤SHG44细胞株,分别在常氧(20%O2)、乏氧(1%O2)12 h和24 h、乏氧+YC-112 h和24 h这5种不同条件下培养,采用Western blot检测HIF-1α的表达水平;细胞克隆形成实验绘制细胞存活曲线以观察其放射敏感性;利用剂量分割法绘制亚致死性损伤修复曲线以观察其修复能力。结果脑胶质瘤SHG44细胞株在乏氧12 h和24 h与常氧培养相比,HIF-1α的表达水平显著升高,放射敏感性下降,其氧增强比分别为1.22和1.37,进一步统计分析发现其亚致死性损伤修复能力升高,且在间隔8、10、12 h照射时,差异均有统计学意义(均P<0.05);而当在乏氧12 h和24 h培养的同时加用YC-1时,HIF-1α的表达水平则显著降低,放射敏感性升高,其增强因子均为1.27,进一步统计分析也发现其亚致死性损伤修复显著降低,且在间隔8、10、12 h照射时,差异均有统计学意义(均P<0.05)。结论 YC-1能明显提高乏氧脑胶质瘤SHG44细胞株的放射敏感性,其机制可能与YC-1能抑制细胞的亚致死性损伤修复能力有关。
Objective To investigate the radiosensitization effect of hypoxia-inducible factor 1α (HIF-1α) inhibitor YC-1 on SHG44 cells and its mechanism. Methods The glioma SHG44 cell line was selected and cultured under 5 different conditions: normoxia (20% O2), hypoxia (1% O2) for 12 h and 24 h, hypoxia + YC-112 h and 24 h The expression of HIF-1α was detected by Western blot. The cell survival curve was drawn to observe the radiosensitivity of cells. The sub-lethal injury repair curve was drawn by dose division method to observe its repair ability. Results Compared with normoxia culture, the expression of HIF-1α in glioma SHG44 cells was significantly increased at 12 h and 24 h after hypoxia, and the radiosensitivity of SHG44 cells decreased. The oxygen uptake ratios were 1.22 and 1.37, respectively. Further statistics Analysis showed that the sublethal injury repair ability was increased, and the difference was statistically significant (P <0.05) at 8, 10 and 12 h intervals, while at 12 h and 24 h after hypoxia With the addition of YC-1, the expression level of HIF-1α was significantly decreased and the radiosensitivity was increased with an enhancement factor of 1.27. Further statistical analysis also found that the sub-lethal injury repair was significantly reduced, and in the intervals of 8,10 , 12 h irradiation, the differences were statistically significant (P <0.05). Conclusion YC-1 can significantly enhance the radiosensitivity of SHG44 cells in hypoxia-induced glioma, which may be related to the ability of YC-1 to inhibit the repair of sublethal cells.