北美海篷子三萜皂苷bigelovii E抑制mTOR信号通路诱导乳腺癌MCF-7细胞凋亡  

Bigelovii E,a triterpenoid compound of Salicornia bigelovii,induced apoptosis of breast cancer MCF-7 cells via inhibiting mTOR/P70S6K/4-EBP signaling

作　　者：黄真真 张丹玉[1] 师琪[1] 管福琴[1] 王奇志[1] 王鸣[1] 冯煦[1] 单宇[1] HUANG Zhen zhen;ZHANG Dan yu;SHI Qi;GUAN Fu qin;WANG Qi zhi;WANG Ming;FENG Xu;SHAN Yu(Institute of Botany, Jiangsu Province and Chinese Academy of Sciences Nanjing210014, China;Jiangsu Province Agricultural Germplasm Resources Protection and Utilization Platform Natural Product Research Center, Nanjing210014, China)

机构地区：[1]江苏省中国科学院植物研究所江苏省农业种质资源保护与利用平台天然产物研究中心,江苏南京210014

出　　处：《中国药理学通报》2017年第12期1655-1660,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81402829);江苏省科技计划项目(No BM2015019)

摘　　要：目的探究北美海篷子的bigelovii E诱导乳腺癌MCF-7细胞凋亡的作用机制。方法使用MTT和集落克隆实验检测bigelovii E对肿瘤细胞增殖的抑制作用;Hoechst33258荧光染色观察bigelovii E作用后细胞形态的改变;流式细胞仪分析bigelovii E对细胞凋亡、细胞线粒体膜电位、细胞ROS水平的影响;Western blot分析线粒体凋亡通路及其调控蛋白表达量的变化。结果 Bigelovii E对乳腺癌细胞MCF-7最敏感;bigelovii E对正常细胞HLF-1毒性较低;bigelovii E抑制乳腺癌MCF-7的集落形成;Hoechst 33258荧光染色检测到bigelovii E诱导的细胞凋亡形态;流式细胞仪检测到bigelovii E引起细胞凋亡和细胞线粒体膜电位下降,并使细胞内ROS水平升高;Western blot表明bigelovii E可通过抑制m TOR磷酸化水平,下调其下游靶点p70S6K、4-EBP的磷酸化水平,进而上调Bax,下调Bcl-xl、Mcl-1蛋白表达,促进线粒体凋亡通路,降低线粒体膜电位,诱发ROS,导致线粒体功能损伤,最终诱导细胞凋亡。结论 Bigelovii E通过m TOR通路调控线粒体凋亡通路,诱导细胞凋亡,具有良好的抗肿瘤效果。AimTo demonstrate that bigelovii E,one of the triterpenoid compounds isolated from Salicornia bigelovii Torr.,induced apoptosis and inhibited proliferation of human breast cancer cells MCF7.MethodsMTT and Clonogenic were used to detect the anti proliferative effect of bigelovii E on human tumor cells.Hoechst33258staining was used to observe the changes of cell morphology in the treatment with bigelovii E.The effect of bigelovii E on cell apoptosis,cell mitochondrial membrane potential and the ROS level was analyzed by flow cytometry.The expression of mitochondrial apoptotic pathway and its regulated proteins were analyzed by Western blot.ResultsBigelovii E was most sensitive to MCF7;bigelovii E had lower toxicity to normal cells HLF1;bigelovii E inhibited the colony formation of breast cancer MCF7;the apoptosis pattern induced by bigelovii E was detected by Hoechst33258;Western blot showed that bigelovii E could down regulate the phosphorylation of mTOR,p70S6K and4EBP,up regulate the expression of Bcl xl and Mcl1proteins,promote the mitochondrial apoptosis pathway,reduce the mitochondrial membrane potential,and induce ROS,leading to mitochondrial function damage,and ultimately inducing apoptosis.ConclusionBigelovii E regulates mitochondrial apoptosis pathway through mTOR pathway,induces apoptosis and has a good anti tumor effect.

关 键 词：北美海篷子 bigeloviiE 乳腺癌 细胞凋亡 MTOR 抗肿瘤 

分 类 号：R284.1[医药卫生—中药学] R329.24[医药卫生—中医学]