共轭亚油酸单体诱导乳腺癌细胞SKBr3凋亡的PPARγ信号通路研究  

Studies on PPARγ Signal Pathway of Conjugated Linoleic Acid Isomers Induce Apoptosis of Human Breast Cancer Cell Line SKBr3

作　　者：袁贤琳[1,2] 何峰[1] 陈青[1] 杨湘玲[1] 杨得坡[1] 王冬梅[1] 钟翎[1] 

机构地区：[1]中山大学药学院,广州510006 [2]广州市中医医院药剂科

出　　处：《生物化学与生物物理进展》2009年第4期491-499,共9页Progress In Biochemistry and Biophysics

基　　金：广东省科技计划项目(2007B031406001,2008A060202010);国家自然科学基金资助项目(30873457)~~

摘　　要：cis9,trans11-CLA和trans10,cis12-CLA是共轭亚油酸(CLA)二种抑瘤活性最强的主要单体.在以前报道二者诱导乳腺癌细胞凋亡的工作基础上,进一步探讨共轭亚油酸单体诱导乳腺癌细胞SKBr3凋亡的途径及机制.采用RT-PCR和Westernblot等方法,证实了CLA在SKBr3细胞中可显著提高PPARγ的转录及蛋白质表达水平,并发现CLA对PPARγ与凋亡相关蛋白Bax、Bcl-2和caspase3的表达影响呈同步相关性,并表现出时间和剂量依赖性.通过PPARγ抑制剂GW9662实验表明它们之间存在协同关系.首次提出了PPARγ-Bcl-2-Caspase3信号通路的SKBr3细胞凋亡途径,为CLA有望作为PPARγ新型调节剂诱导肿瘤细胞凋亡在临床应用提供实验证据.Cis9, trans 11 and trans 10, cis 12-CLA are two major isomers of conjugated linoleic acid, which have stronger activities of anti-tumor. Based the previous studies, it was explored the pathway and mechanism of inducing apoptosis in human breast cancer cell line SKBR3 by c9, t11-CLA and tl0, c l2-CLA. It was confirmed that CLA could increase obviously the transcription and protein expression levels of PPARγ by RT-PCR and Western blot. The synchronism and correlation between PPARγ and apoptotic proteins Bax, Bcl-2, caspase3 changes were found with a dose- and time-dependent manner. PPARγ inhibitor GW9662 experimental result showed that there is cooperative relation between them. This is the first report that CLA induces apoptosis in SKBr3 cell by the signal pathway of PPARγ-Bcl-2-Caspase3. These observations indicated that CLA will be useful for clinic therapy of anti-tumor as a new regulator of PPARγ in the future.

关 键 词：共轭亚油酸单体 过氧化物酶体增殖蛋白激活受体γ 细胞凋亡 人乳腺癌细胞系SKBr3 

分 类 号：Q291[生物学—细胞生物学] R91[医药卫生—药学]