刘务玲,姚尧,陈娟,吴昌学,宋晶睿,王春林,邱剑飞,王立平,朱伟明,龙群,李艳梅
LIU Wuling,YAO Yao,CHEN Juan,WU Changxue,SONG Jingrui,WANG Chunlin,QIU Jianfei,WANG Liping,ZHU Weiming,LONG Qun,LI Yanmei

• 1:贵州省中国科学院天然产物化学重点实验室
• 2:贵州医科大学
• 3:中国海洋大学

摘要(Abstract)：

目的:探讨双吲哚马来酰亚胺衍生物GZWM-051诱导人白血病HEL细胞凋亡的作用及机制。方法:分别使用不同浓度的GZWM-051处理HEL细胞,采用MTT法测定HEL细胞的存活率,计算抑制率及IC_(50)值;采用Hoechst 33258染色观察处理HEL细胞24 h时的凋亡现象,采用流式细胞术检测处理HEL细胞24及48 h时细胞凋亡水平,Western blot法检测处理HEL细胞24 h时细胞凋亡蛋白表达水平。结果:GZWM-051能抑制HEL细胞的增殖活性,显著提高其凋亡率(P<0.01);Western blot结果显示,0.050μmol/L或0.100μmol/LGZWM-051处理HEL细胞后,其Bcl-2蛋白表达水平显著下调(P<0.01),Caspase-3剪切体表达水平显著上调(P<0.01)。结论:GZWM-051可能是通过下调抗凋亡蛋白Bcl-2表达水平和激活Caspase-3剪切体水平诱导HEL细胞凋亡。
Objective: This study aimed to assess the effect and mechanism of diindole maleimide derivative GZWM-051 on HEL cell apoptosis in patients with leukemia. Methods: HEL cell was treated with different concentrations of compounds and the cell viability was measured by MTT method. OD value was recorded and the inhibition rate and IC_(50) value were calculated. Apoptosis of cell was detected by Hoechst 33258 kit at 24 h. Cell apoptosis level was analyzed by fowcytometry at 24 h and 48 h, and relevant protein expression level was detected by western blot at 24 h. Results: GZWM-051 signi-ficantly inhibited the proliferation of HEL cell line and induced cell apoptosis(P<0.01). The expression level of Bcl-2 was down-regulated(P<0.01), while the expression level of cleaved caspase-3 was up-regulated(P<0.01) after HEL cell line was treated with 0.05 μmol/L or 0.1 μmol/L of GZWM-051. Conclusion: Gzwm-051 may induce HEL cell apoptosis by down-regulating the expression level of anti-apoptotic protein bcl-2 and activating the caspase-3.

关键词(KeyWords)： 白血病;双吲哚马来酰亚胺衍生物;HEL细胞系;凋亡;米哚妥林;半胱氨酸天冬氨酸蛋白
leukemia;bisindolylmaleimide derivative;HEL cell line;apoptosis;midostaurin;caspase-3

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金(81700169)

作者(Author): 刘务玲,姚尧,陈娟,吴昌学,宋晶睿,王春林,邱剑飞,王立平,朱伟明,龙群,李艳梅
LIU Wuling,YAO Yao,CHEN Juan,WU Changxue,SONG Jingrui,WANG Chunlin,QIU Jianfei,WANG Liping,ZHU Weiming,LONG Qun,LI Yanmei

DOI: 10.19367/j.cnki.1000-2707.2019.09.002

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