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机构地区:[1]上海交通大学医学院附属新华医院血液科,上海200092
出 处:《上海交通大学学报(医学版)》2017年第6期738-743,共6页Journal of Shanghai Jiao tong University:Medical Science
基 金:上海市教育委员会高峰高原学科建设计划(20152219);上海市教育委员会资助项目(13ZZ084)~~
摘 要:目的·探讨藤黄酸(GA)对NK/T细胞淋巴瘤(NK/TCL)细胞株SNK-1、SNK-6和SNT-8诱导凋亡的作用及其可能机制。方法·以不同浓度GA处理SNK-1、SNK-6和SNT-8细胞株24 h,CCK-8法测定GA对细胞活力的影响;Annexin V-FITC/PI流式细胞术检测细胞凋亡;Western blotting方法检测凋亡和信号通路相关蛋白及磷酸化的变化。结果·CCK-8法检测结果显示GA对3株细胞活力均有显著抑制作用。流式细胞术检测结果显示,GA诱导3株细胞凋亡。Western blotting检测结果显示GA处理的细胞出现caspase-3和caspase-9的活化及PARP的剪切,且Bcl-xl表达下降。信号通路蛋白STAT3的磷酸化水平在SNK-1和SNT-8中显著下调,ERK1/2的磷酸化水平在SNK-1和SNK-6中显著下调。结论·GA对NK/TCL细胞株SNK-1、SNK-6和SNT-8有显著的诱导凋亡效应,抗凋亡蛋白Bcl-xl以及JAKs/STATs、MEK/MAPK信号通路可能参与了这一过程。Objective · To identify the effect and potential mechanism of gambogic acid (GA) on natural killer/T-cell lymphoma (NK/TCL) cell lines. Methods · SNK-1, SNK-6 and SNT-8 were incubated with various concentrations of GA for 24 h, and cell viability was detected with CCK-8 assay. Cell apoptosis was examined by Annexin V-FITC/PI staining assay. Levels of proteins regulating cell apoptosis and phosphorylation levels of proteins in key signaling pathways were detected by Western blotting. Results · GA showed a potent effect on reduction of cell viability of NK/TCL cell lines in CCK-8 assay. GA increased the percentages of Annexin V positive cells and induced activation of caspase-3 and caspase-9, cleavage of PARP as well as the reduction of Bcl-xl. GA also inhibited the phosphorylation levels of STAT3 in SNK-1 and SNT-8, and ERK1/2 in SNK-1 and SNK-6 significantly. Conclusion · GA induces cell apoptosis in NK/TCL cell lines SNK-1, SNK-6 and SNT-8. Anti-apoptosis protein Bcl-xl and signaling pathway JAKs/ STATs and MEK/MAPK might be involved in this process.
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