自噬对人胆管癌HCCC-9810细胞^(125)I粒子内放疗敏感性的影响

The effect of autophagy on the radioresistance of human cholangiocarcinoma HCCC-9810 cell with ^(125)I seeds

目的:探讨自噬对人胆管癌HCCC-9810细胞125I粒子内放疗敏感性的影响。方法:用MTT检测不同照射剂量下125I粒子对HCCC-9810细胞增殖活性的影响。通过电镜检测自噬体变化,用Western blot检测LC3来观察不同照射剂量下125I粒子对HCCC-9810细胞自噬发生的影响。3-MA抑制自噬后检测125I粒子对HCCC-9810细胞增殖活性的影响。结果:125I粒子照射HCCC-9810细胞后细胞活性明显下降并呈剂量相关性。电镜检测和LC3-Ⅱ蛋白印迹显示内放疗照射后HCCC-9810细胞自噬明显增加。3-MA抑制自噬后125I粒子内放疗对HCCC-9810细胞的抑制作用显著增强。结论:125I粒子内放疗后HCCC-9810细胞自噬明显增加,抑制自噬后125I粒子内放疗对HCCC-9810细胞生长的抑制作用显著增强。

Objective:To investigate the role of autophagy in 125 I seeds brachytherapy-induced cytotoxicity in hu-man HCCC-9810 cells.Methods:The growth inhibition of HCCC-9810 cells induced by brachytherapy with 125 I seeds was assessed with methyl thialy terazolium (MTT)assay.The effects of 125 I seeds on autophagy were observed with electron microscopy (EM)and microtubule -associated protein 1 light chain 3 (LC3 )detected by Western blot.The autophagic inhibitor 3 -methylademine (3 -MA)was used to characterize the effect of autophagy on the brachytherapy-induced cytotoxicity.Results:Brachytherapy with low dose rate of 125 I seeds decreased the viability of HCCC-9810 cells in a dose-dependent manner.Autophagy induced by brachytherapy was evidenced by EM.West-ern blot analysis indicated that brachytherapy with low dose rate of 125 I seeds also augmented the inhibitory effect of brachytherapy with 125 I seeds on the sensitization of HCCC-9810 cells.Conclusion:Brachytherapy with 125 I seeds in-duces autophagy in human HCCC-9810 cells and autophagic inhibitors can increase the cytotoxicity of brachytherapy to cholangiocarcinoma cells.