抑制HIF-1ɑ对胰腺癌MIA-Paca2细胞辐射敏感性影响及相关机制研究

Effect of HIF-1α inhibition on radiosensitivity of pancreatic cancer MIA-Paca2 cells and its related mechanisms

目的通过观察辐射与HIF-1ɑ抑制剂联合应用对胰腺癌MIA-PaCa2细胞凋亡及HIF-1ɑ、VEGF蛋白表达的影响,初步探索HIF-1ɑ及VEGF在胰腺癌的辐射增敏中的作用及相关机制。方法 Annexin V/PI检测凋亡细胞,观察不同干预方式对细胞凋亡的影响;Western Blot法检测HIF-1ɑ、VEGF的表达情况;细胞辐射使用^(60)Co-γ射线进行照射。结果联合治疗后的细胞凋亡率高于其他各组(P <0.05);辐射可促进HIF-1ɑ及VEGF蛋白表达;相较于单纯辐射处理,辐射前予HIF-1ɑ抑制剂YC-1处理可下调VEGF的表达。结论 HIF-1ɑ抑制剂联合电离辐射能协同促进胰腺癌MIA-Paca2细胞凋亡,其机制可能是通过抑制HIF-1ɑ,使VEGF表达下调,降低其对辐射损伤的保护作用,同时诱导肿瘤细胞的凋亡,增强放射线的杀伤作用,提高胰腺癌细胞的放射敏感性。

Objective By observing the effect of radiation combined with HIF-1αinhibitor on apoptosis of MIA-PaCa2 cells and expression of HIF-1αand VEGF proteins in pancreatic cancer, and to explore the role of HIF-1αand VEGF in radiosensitization of pancreatic cancer and its related mechanisms preliminarily. Methods Cell apoptosis was analyzed by AnnexinV/PI, the effects of different intervention methods on cell apoptosis were observed. The expressions of hypoxia-inducible factor-1ɑ（HIF-1α and vascular endothelial growth factor（VEGF） were detected by Western Blot. And the radiation was conducted by 60Co-γ. Results apoptosis rate after combined treatment was higher than that in other groups（P 〈0.05）. Radiation can promote HIF-1αand VEGF protein expression. Pretreatment with HIF-1 inhibitor YC-1 can reduce the expression of VEGF compared with radiation alone. Conclusion The combination of radiation and HIF-1αinhibitor can promote apoptosis of pancreatic cancer MIA-Paca2 cells. The mechanism may be through inhibiting HIF-1α down-regulating the expression of VEGF, reducing its protective effect on radiation injury, inducing apoptosis of tumor cells, enhancing the killing effect of radiation, and enhancing the radiosensitivity of pancreatic cancer cells.