贵州医科大学学报

2019, v.44;No.228(09) 993-998

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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

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;The Key Laboratory of Chemistry for Natural Products of Guizhou Province, Chinese Academy of Sciences;Guizhou Medical University;Ocean University of China;

摘要(Abstract):

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、0.100μmol/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 CD41 a 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(KeyWords): 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
leukemia;bisindolylmaleimide derivative;differentiation;G2 phase arrest;signal transducer and activator of transcription-3;human erythroleukemia cell line

Abstract:

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基金项目(Foundation): 国家自然科学基金项目(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;The Key Laboratory of Chemistry for Natural Products of Guizhou Province, Chinese Academy of Sciences;Guizhou Medical University;Ocean University of China;

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DOI: 10.19367/j.cnki.1000-2707.2019.09.001

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