大黄素提高HeLa细胞对三氧化二砷促凋亡敏感性的研究  

EMODIN SENSITIZES HELA CELL TO ARSENIC TRIOXIDE INDUCED APOPTOSIS VIA THE REACTIVE OXYGEN SPECIES-MEDIATED SIGNALING PATHWAYS

作　　者：杨洁[1] 汤雪明[1] 李慧[1] 史桂英[1] 朱平[1] 金慧芳[1] 易静[1] 

机构地区：[1]上海第二医科大学细胞生物学教研室,上海200025

出　　处：《实验生物学报》2003年第6期465-475,共11页Acta Biologiae Experimentalis Sinica

基　　金：国家自然科学基金(30170475)

摘　　要：活性氧(reactive oxygen specis ROS)在三氧化二砷(arsenic trioxide,As_2O_3)诱导肿瘤细胞凋亡中扮演重要角色。本研究用一种天然蒽醌类物质——大黄素(emodin)作为提高HeLa细胞ROS水平的手段,考察其对As_2O_3促凋亡敏感性的影响,并探究可能涉及的信号传导机制。结果显示大黄素10μmol/L提高ROS并增加了HeLa细胞在As_2O_32μmol/L作用下的凋亡率,对正常成纤维细胞却无影响。该联合作用可以促进HeLa细胞线粒体跨膜电位降低;抑制转录因子NF-kB激活。本研究提示:大黄素通过提高ROS介导凋亡信号传导的增强和生存信号传导的抑制,增加HeLa细胞对As_2O_3促凋亡的敏感性。Since reactive oxygen species(ROS) has been known to play an important role in apop-tosis induced by arsenic trioxide,we attempt to elevate the cellular ROS level on HeLa cell by an natural anthraquinone-emodin.then to study its effect on apoptotic sensitivity to arsenic,and finally to investigate the mechanisms of the involved signaling pathway. The results showed that emodin 10 micro-mol/L could enhance arsenic induced apoptosis via generation of ROS, whereas rendered no detectable effect on normal fibroblast. Increased ROS promoted mitochondrial transmembrane potential collapse; inhibited the activation of transcription factors NF-kappa B. The study elucidated that emodin sensitize HeLa cells via generation of ROS which result in enhancement of apoptosis signaling pathway and inhibition of survival signaling pathway.

关 键 词：大黄素 HELA细胞 三氧化二砷 凋亡 敏感性 ROS 信号传导 

分 类 号：R73-3[医药卫生—肿瘤]