文章摘要
王桂明 杨婵 鲁阳芳 谷雪 王彦 闫超.去氢木香内酯干预人乳腺癌MCF-7细胞机制的探究[J].,2015,15(34):6601-6605
去氢木香内酯干预人乳腺癌MCF-7细胞机制的探究
Study on Mechanismof Dehydrocostus Lactone Treatment on Breast CancerMCF-7 Cells
  
DOI:
中文关键词: 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
英文关键词: MCF-7 cells  Dehydrocostus lactone  Apoptosis  Cell metabonomics  MMP
基金项目: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)
作者单位
王桂明 杨婵 鲁阳芳 谷雪 王彦 闫超 上海交通大学药学院 
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中文摘要:
      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、8 滋g/mL)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。
英文摘要:
      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 ug/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.Conclusion: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.
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