双吲哚马来酰亚胺衍生物GZWM-051对HEL细胞周期及分化的影响  

Effect of Bisindolylmaleimide Derivative GZWM-051 on HEL Cell Cycle and Differentiation

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, Chinese Academy of Sciences, Guiyang 550014, Guizhou, China;Guizhou Medical University, Guiyang 550025, Guizhou;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993-998,共6页Journal of Guizhou Medical University

基　　金：国家自然科学基金项目(81700169)

摘　　要：目的:研究双吲哚马来酰亚胺衍生物GZWM-051(简称化合物GZWM-051)对人白血病HEL细胞周期及分化的影响。方法: HEL细胞分为对照组(DMSO处理)和化合物GZWM-051组(0.025、0.050、0.100 μmol/L化合物GZWM-051处理,分别为低剂量、中剂量、高剂量组),采用流式细胞术检测细胞周期及分化水平,采用Western blot法检测细胞Cyclin B1、c-Myc、STAT3及P-STAT3蛋白表达水平。结果:处理24 h后,与对照组HEL细胞相比,化合物GZWM-051中、高剂量组 HEL细胞处于G1和S期细胞数量显著减少,处于G2期的数量显著增加,差异有高度统计学意义( P <0.01);相比对照组,作用48 h后化合物GZWM-051低、中、高剂量组HEL细胞的CD41a和CD71均上调;与对照组HEL细胞对比,中剂量及高剂量化合物GZWM-051组HEL细胞生长相关蛋白c-Myc表达水平降低,差异有统计学意义( P <0.05或 P <0.01);与对照组HEL细胞对比,低、中及高剂量的化合物GZWM-051组HEL细胞的P-STAT3表达水平降低( P <0.05或 P <0.01),中、高剂量化合物GZWM-051组HEL细胞周期蛋白Cyclin B1表达水平降低( P <0.05)。结论:化合物GZWM-051不仅能诱导白血病HEL细胞发生G2周期阻滞,促进其向巨核及红系进行分化,抑制细胞恶性增殖,还能失活STAT3关键通路。Objective: To study the effect of bisindolylmaleimide derivative GZWM-051 (abbreviated as compound GZWM-051) on cell cycle and differentiation of human leukemia HEL cells. Methods: HEL cells were divided into control group (DMSO treatment) and treatment groups (low dose 0.025, medium dose 0.050, high dose 0.100 μmol/L compound GZWM-051). Cell cycle and differentiation were assayed using flow cytometry, The expression levels of Cyclin B1, c-Myc, STAT3 and P-STAT3 were detected by Western blot. Results: After treatment for 24 h, compared with control group, the cell numbers in G1 and S phases were significantly decreased in medium and high dose groups, while the cell numbers in G2 phase were remarkably increased( P <0.01). At 48 h after the treatment, the expression levels of CD41a and CD71 were upregulated relative to control group, while the expression levels of c-MYC and Cyclin B1 was downregulated in both medium and high dose treatment ( P <0.05 or P <0.01, P <0.05 ). In addition, the treatment downregulated phosphorylation levels of STAT3 ( P <0.05 or P <0.01). Conclusion: Compound GZWM-051 can not only induce G2 cycle arrest and differentiation in leukemia HEL cells , but also inactivate STAT3.

关 键 词：白血病 双吲哚马来酰亚胺衍生物 分化 G2期阻滞 信号转导子和转录激活子3 人红白血病细胞系 

分 类 号：R915[医药卫生—微生物与生化药学]