去氢木香内酯干预人乳腺癌MCF-7细胞机制的探究  

Study on Mechanism of Dehydrocostus Lactone Treatment on Breast Cancer MCF-7 Cells

作　　者：王桂明[1] 杨婵[1] 鲁阳芳[1] 谷雪[1] 王彦[1] 闫超[1] 

机构地区：[1]上海交通大学药学院,上海200240

出　　处：《现代生物医学进展》2015年第34期6601-6605,共5页Progress in Modern Biomedicine

基　　金：国家自然科学基金项目(21175092;21105064);国家重大科学仪器设备开发专项(2011YQ150072;2011YQ15007204;2011YQ15007207;211YQ15007210);上海市自然科学基金项目(12ZR1413600)

摘　　要：目的:探讨去氢木香内酯对乳腺癌MCF-7细胞凋亡、线粒体跨膜电位及代谢物的影响,为研究去氢木香内酯诱导MCF-7细胞凋亡的作用机制提供新的视角。方法:采用流式细胞仪测定不同浓度去氢木香内酯(0、2、4、8μg/m L)对MCF-7细胞凋亡及线粒体跨膜电位的影响;GC-TOFMS测定去氢木香内酯作用前后,MCF-7细胞内具有显著性变化的代谢差异物。结果:研究结果表明,去氢木香内酯能诱导MCF-7细胞的凋亡、促进线粒体跨膜电位的降低;正交偏最小二乘法判别分析(OPLS-DA)多维统计方法对代谢组学数据分析得到柠檬酸、D-核糖、脯氨酸、苯丙氨酸、赖氨酸等16种代谢差异物。结论:推测去氢木香内酯通过引起线粒体跨膜电位降低而破坏了线粒体的结构,进一步阻碍了线粒体的功能,导致了细胞内代谢物的紊乱,最终诱导了细胞的凋亡。Objective： This study aims to investigate the effects of dehydrocostus lactone on apoptosis, mitochondrial membrane potential （MMP） and intracellular metabolites of MCF-7 cells and to explore the mechanism of apoptosis promoted by Dehydrocostus lactone. Methods： In vitro experiments, the effects of dehydrocostus lactone with different concentrations （i.e. 0, 2, 4, 8 μg/mL） on the apoptosis and MMP of MCF-7 cells were investigated by flow cytometry. Furthermore, we examined the differences in metabolic profiles between control and drug-treated with GC-TOFMS. Results： Significant induction of apoptosis was detected in MCF-7 cells. Moreover, dehydrocostus lactone could also promote the decline of MMP. Orthogonal partial least squares discriminant analysis （OPLS-DA） was used to process the metabolic data. A total of sixteen metabolites such as citric acid, D-ribose, L-proline, phenylalanine, L-lysine were preliminarily identified as differential metabolites. Conclusions： These results indicated that dehydrocostus lactone may destroy the mitochondria structure by disrupting MMP. The destroyed mitochondrial disturbed the balance of metabolites in MCF-7 cells and thus induced the apoptosis of MCF-7 cells.

关 键 词：MCF-7细胞 去氢木香内酯 细胞凋亡 细胞代谢组学 线粒体跨膜电位 

分 类 号：R737.9[医药卫生—肿瘤]