薇甘菊内酯衍生物LY19380b对人白血病细胞HEL的作用及机制研究  

The effect and mechanism of a novel mikanolide derivative LY19380b on human leukemia cell HEL

作　　者：饶青 刘晟 黄磊[1,3] 李艳梅 郑江 RAO Qing;LIU Sheng;HUANG Lei;LI Yanmei;ZHENG Jiang(State Key Laboratory of Functions and Applications of Medicinal Plants,Guizhou Medical University,Guiyang 550014,Guizhou,China;School of Pharmacy,Guizhou Medical University,Guiyang 550025,Guizhou,China;Department of Pharmacological Activity Screening,Natural Products Research Center of Guizhou Province,Guiyang 550014,Guizhou,China)

机构地区：[1]贵州医科大学药用植物功效与利用国家重点实验室,贵州贵阳550014 [2]贵州医科大学药学院,贵州贵阳550025 [3]贵州省天然产物研究中心药理与生物活性研究所,贵州贵阳550014

出　　处：《中国现代医生》2024年第19期1-7,共7页China Modern Doctor

基　　金：贵州省自然科学基金资助项目(黔科合基础-ZK[2022]一般293)。

摘　　要：目的 研究薇甘菊内酯衍生物LY19380b对人白血病细胞HEL的作用及机制。方法 四甲基偶氮唑蓝(methyl thiazolyl tetrazolium,MTT)法检测LY19380b对不同的人肿瘤细胞的抗增殖活性,利用流式细胞术测定细胞周期,Annexin V-FITC/PI和Hoechst 33258染色测定细胞凋亡;Western blot分析LY19380b对细胞凋亡及周期相关蛋白的影响。结果 LY19380b对不同的人肿瘤细胞均具有抗增殖活性,对人白血病细胞HEL具有显著的生长抑制作用,可诱导HEL细胞发生凋亡并导致细胞周期阻滞;此外,LY19380b作用于HEL细胞后显著增加P53、BIM、BID、BAD、BAX、FLIP、P21及Cyclin B1蛋白的表达,降低Bcl-2、p-CDC25C、p-AKT、p-STAT3、p-ERK蛋白的表达。结论 LY19380b通过增加促凋亡蛋白BIM、BID、BAD、BAX的表达,降低抗凋亡蛋白Bcl-2的表达,诱导人白血病细胞HEL发生凋亡,上调周期蛋白P21、Cyclin B1的表达,从而导致HEL细胞周期阻滞。Objective To investigate the mechanism of mikanolide derivative LY19380b in inhibiting the growth of human leukemia cell HEL.Methods Methyl thiazolyl tetrazolium(MTT) assay was used to detect the effect of compound LY19380b on the proliferation of human tumor cells,flow cytometry was used to determine cell cycle,Annexin V-FITC/PI double staining and Hoechst 33258 staining were used to determine apoptosis.Western blot was used to analyze effects of LY19380b on cell cycle and apoptosis-related proteins.Results LY19380b had anti-proliferative activity on different human tumor cells,and significantly inhibited the growth of human leukemia cell HEL.It can also induce apoptosis and affect the cell cycle of HEL.In addition,LY19380b could significantly increase the expressions of P53,BIM,BID,BAD,BAX,FLIP,P21 and Cyclin B1 proteins,while decreased the expressions of Bcl-2,p-CDC25C,p-AKT,p-STAT3 and p-ERK proteins.Conclusion By increasing the expressions of pro-apoptotic proteins BIM,BID,BAD and BAX,decreasing the expression of anti-apoptotic protein Bcl-2,LY19380b induced the apoptosis of human leukemia cell HEL,and upregulated the expressions of P21 and Cyclin B1,thus leading to cell cycle arrest in HEL.

关 键 词：白血病 薇甘菊内酯 凋亡 机制 

分 类 号：R979.1[医药卫生—药品]