二蒿乙醚基胺马来酸盐诱导活性氧产生促进SU-DHL-4细胞凋亡  

Artemisinin derivative SM1044 promotes apoptosis of SU-DHL-4 cells by inducing reactive oxygen species

作　　者：苗圣超 程春艳[1] 赵玲玲[1] 王涛[1] 宋志群[1] 崔雯[1] 彭丽君[1] 王瑾[1] 李英[2] 王月英[1] 糜坚青[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院血液科上海血液学研究所系统生物医学协同创新中心,上海200025 [2]中国科学院上海药物研究所,上海201203

出　　处：《内科理论与实践》2015年第4期284-288,共5页Journal of Internal Medicine Concepts & Practice

基　　金：上海市教育委员会科研创新重点项目(项目编号:13zz088)

摘　　要：目的:研究青蒿素衍生物二蒿乙醚基胺马来酸盐(SM1044)诱导活性氧产生促进SU-DHL-4细胞凋亡的机制。方法:流式细胞术检测SM1044对SU-DHL-4细胞活性氧的水平影响;流式细胞术检测SU-DHL-4细胞的凋亡情况及蛋白质印迹检测凋亡相关蛋白的表达;免疫荧光技术检测细胞内钙离子的荧光强度及蛋白质印迹检测内质网应激相关蛋白CCAAT/增强子结合蛋白(C/EBP)腺苷环磷酸反应元件结合转录因子同源蛋白(CHOP)的表达。结果:SM1044可诱导SU-DHL-4细胞产生活性氧,且具有时间依赖性(r=0.951,P=0.003);SM1044可诱导SU-DHL-4细胞凋亡及凋亡相关蛋白的活化,使用N-乙酰半胱氨酸(NAC)清除活性氧后,SM1044诱导SU-DHL-4细胞凋亡的作用被抑制(P<0.01),凋亡相关蛋白的表达也被抑制;SM1044可促进SU-DHL-4细胞内钙离子水平的升高以及内质网应激相关蛋白CHOP的表达,使用NAC清除活性氧后,钙离子水平的升高以及CHOP蛋白的表达被抑制。结论:SM1044可通过诱导SU-DHL-4细胞产生活性氧促进SU-DHL-4细胞凋亡,其机制可能与活性氧激活钙离子-内质网应激有关。Objective To investigate the mechanism of induction of apoptosis of diffuse large B-cell lymphoma cell line SU-DHL-4 via inducing reactive oxygen species by artemisinin derivative SM1044. Methods Flow cytometry was per- formed to detect the reactive oxygen species induced by SM1044 in SU-DHL-4 cells. Cell apoptosis was assessed with flow cytometry, and expression of apoptosis related proteins was determined by Western blotting. Immunofluorescence was per- formed to measure the level of intraeellulaT calcium and Western blotting was performed to detect the expression of apop- tosis related proteins. Results SM1044 could induce reactive oxygen species in SU-DHL-4 cells in a dose and time de- pendent manner （r=0.951, P=0.003）, and SM1044 could induce apoptosis and expression of apoptosis-related proteins in SU-DHL-4 cells. After using N-acetyl-L-cysteine （NAC） for scavenging reactive oxygen species, the apoptosis and expres- sion of apoptosis-related proteins in SU-DHL-4 cells induced by SM1044 were inhibited （/~〈0.01）. The level of intracellular calcium was significantly enhanced by SM1044, as well as the expression of endoplasmie reticulum stress related proteins CCAAT/enhancer-binding protein homologous protein （CHOP）. After using NAC for scavenging reactive oxygen species, the level of intracellnlar calcium was significantly decreased, so as the expression of endoplasmic reticulum stress related proteins CHOP. Conclusions SMl044 could significantly induce the apoptosis of SU-DHL-4 cells by promoting the release of reactive oxygen species which might elevate the level of intracellular calcium and endoplasmic reticulum stress.

关 键 词：青蒿素衍生物 弥漫大B细胞淋巴瘤 活性氧 细胞凋亡 

分 类 号：R733.1[医药卫生—肿瘤]