双吲哚马来酰亚胺衍生物GZWM-051诱导白血病细胞凋亡的作用及机制  

Effect of Bisindolylmaleimide Derivative GZWM-051 on HEL Cell Apoptosis and Its Mechanism in Patients with Leukemia

作　　者：刘务玲 姚尧[1,2] 陈娟 吴昌学[2] 宋晶睿[1,2] 王春林[1,2] 邱剑飞 王立平 朱伟明 龙群[1,2] 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(The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences,Guiyang 550014, Guizhou, China;Guizhou Medical University, Guiyang 550025, Guizhou, China;Ocean University of China, Qingdao 266100, Shandong, China)

机构地区：[1]贵州省中国科学院天然产物化学重点实验室,贵州贵阳550014 [2]贵州医科大学,贵州贵阳550025 [3]中国海洋大学,山东青岛266100

出　　处：《贵州医科大学学报》2019年第9期999-1004,共6页Journal of Guizhou Medical University

基　　金：国家自然科学基金(81700169)

摘　　要：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,0.050 μmol/L或0.100 μmol/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：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水解酶3 

分 类 号：R915[医药卫生—微生物与生化药学]