去氢木香内酯干预人乳腺癌MCF-7细胞机制的探究

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。

Study on Mechanismof Dehydrocostus Lactone Treatment on Breast CancerMCF-7 Cells

Objective:This study aims to investigate the effects of dehydrocostus lactone on apoptosis, mitochondrial membranepotential (MMP) and intracellular metabolites of MCF-7 cells and to explore the mechanism of apoptosis promoted by Dehydrocostuslactone.Methods:In vitro experiments, the effects of dehydrocostus lactone with different concentrations (i.e. 0, 2, 4, 8 ug/mL) on theapoptosis and MMP of MCF-7 cells were investigated by flow cytometry. Furthermore, we examined the differences in metabolic profilesbetween 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) wasused to process the metabolic data. A total of sixteen metabolites such as citric acid, D-ribose, L-proline, phenylalanine, L-lysine werepreliminarily identified as differential metabolites.Conclusion:These results indicated that dehydrocostus lactone may destroy themitochondria structure by disrupting MMP. The destroyed mitochondrial disturbed the balance of metabolites in MCF-7 cells and thusinduced the apoptosis of MCF-7 cells.