氯喹通过抑制自噬促进TRAIL诱导的胶质瘤细胞凋亡

发布时间：2017-12-28 17:04

本文关键词：氯喹通过抑制自噬促进TRAIL诱导的胶质瘤细胞凋亡　出处：《中国临床神经外科杂志》2016年04期 　论文类型：期刊论文

【摘要】：目的探讨氯喹对肿瘤坏死因子相关凋亡诱导配体(TRAIL)诱导的胶质瘤细胞凋亡的影响。方法体外培养人脑胶质瘤细胞U251和Hela细胞,分为对照组、氯喹组、重组人TRAIL蛋白(rhTRAIL)组和联用组(氯喹与rhTRAIL联合应用);MTT法检测细胞活力,Annexin V-FITC/PI凋亡检测试剂盒检测细胞凋亡,共聚焦显微镜检测GFP-LC3的分布判断细胞自噬水平,Western Blot检测cleaved caspase-8的表达水平。结果氯喹和rhTRAIL均显著增加U251细胞和Hela细胞自噬水平,而且联用较单独应用自噬水平更高,Hela细胞自噬水平明显高于U251细胞。U251细胞和Hela细胞增殖抑制率和细胞凋亡率:氯喹组与对照组均无统计学差异(P0.05),rhTRAIL和联用组均明显高于氯喹组(P0.05),联用组明显高于rhTRAIL组(P0.05)。氯喹组和对照组Cleaved caspases-8水平无统计学差异(P0.05),rhTRAIL和联用组均明显增高(P0.05),联用组明显高于rhTRAIL组(P0.05)。结论氯喹能通过抑制细胞自噬,增强TRAIL诱导的U251细胞凋亡。
[Abstract]:Objective to investigate the effect of chloroquine on the apoptosis of glioma cells induced by tumor necrosis factor related apoptosis inducing ligand (TRAIL). Cultured human glioma cells U251 and Hela cells in vitro, divided into control group, chloroquine group, recombinant human TRAIL protein (rhTRAIL) group and combination group (combination of chloroquine and rhTRAIL); MTT assay for cell viability, apoptosis detection Annexin V-FITC/PI apoptosis detection kit, total distribution of detection of GFP-LC3 confocal microscopy to determine the level of autophagy and the expression level of Western Blot detection of cleaved caspase-8. Results chloroquine and rhTRAIL significantly increased the autophagy level of U251 cells and Hela cells, and the level of autophagy was higher than that of autophagy alone. The autophagy level of Hela cells was significantly higher than that of U251 cells. U251 cell and Hela cell proliferation inhibition rate and apoptosis rate: there was no significant difference between chloroquine group and control group (P0.05), rhTRAIL and combination group were significantly higher than those in chloroquine group (P0.05), and the combination group was significantly higher than that in rhTRAIL group (P0.05). There was no significant difference in Cleaved caspases-8 level between chloroquine group and control group (P0.05), rhTRAIL and combined group were significantly higher (P0.05), and the combined group was significantly higher than that of rhTRAIL group (P0.05). Conclusion chloroquine can enhance the apoptosis of U251 cells induced by TRAIL by inhibiting autophagy.
【作者单位】：武汉大学中南医院神经外科;十堰市太和医院神经外科;
【分类号】：R739.4
【正文快照】： 肿瘤坏死因子相关凋亡诱导配体(tumor necro-sis factor-related apoptosis-inducing ligand,TRAIL)可诱导细胞凋亡[1]。但是,随着研究的深入,TRAIL抵抗的出现成为TRAIL临床应用的障碍。研究发现TRAIL抵抗的肿瘤细胞株自噬水平明显高于TRAIL敏感的肿瘤细胞株[2]。凋亡和自噬密

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