木香烃内酯诱导乳腺癌MCF-7细胞凋亡作用机制的研究  

Study on Mechanism of Costunolide-induced Apoptosis in Breast Cancer MCF-7 Cells

作　　者：王桂明[1] 史栋栋 彭章晓[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：《分析化学》2015年第5期682-688,共7页Chinese Journal of Analytical Chemistry

基　　金：国家自然科学基金项目(Nos.21175092;21105064);国家重大科学仪器设备开发专项(Nos.2011YQ150072);上海市自然科学基金项目(No.12ZR1413600)资助~~

摘　　要：研究了木香烃内酯诱导人乳腺癌细胞MCF-7细胞凋亡的作用机制。采用流式细胞仪测定不同浓度木香烃内酯(0,2,4,8μg/m L)作用于MCF-7细胞后细胞凋亡、活性氧(Reactive oxygen species,ROS)含量及线粒体跨膜电位(Mitochondrial transmembrane potential,MTP)的变化,气相色谱-质谱联用(GC-TOF/MS)技术分析加药组与未加药组的代谢差异物。结果表明,木香烃内酯能诱导MCF-7细胞凋亡,并具有浓度依赖性,能够促使ROS含量升高;MTP在2μg/m L木香烃内酯作用时升高,在4和8μg/m L时显著下降;基于GC-TOF/MS的细胞代谢组学研究,最终发现15种代谢差异物。基于上述结果,推测木香烃内酯通过引起ROS含量升高、MTP降低,扰乱线粒体的正常功能,进一步阻碍TCA循环,抑制ATP合成,扰乱了细胞内代谢物的平衡,并引起位于膜间隙的凋亡相关蛋白释放,最终导致MCF-7细胞的凋亡。This study aimed to investigate the mechanism of costunolide-induced apoptosis in breast cancer MCF-7 cells. The effects of costunolide at different concentration levels （2, 4 and 8 μg/mL） on the apoptosis, reactive oxygen species （ROS） and mitochondrial transmembrane potential （MTP） of MCF-7 cells were investigated by flow cytometry. The differences in metabolic profiles between control and drug-treated cells were examined by GC-TOF/MS. Significant apoptosis was detected in MCF-7 cells, accompanied by the overproduction of ROS. The MTP increased at 2 μg/mL and decreased at 4 and 8 μg/mL of costunolide. A total of 15 differential metabolites were identified from metabolomics analysis. These results indicated that the function of mitochondria might be interfered with costunolide by increasing the ROS and decreasing MTP. Then, tricarboxylic acid （TCA） cycle and the synthesis of adenosine triphosphate （ATP） were blocked, and the metabolic balance was disturbed. Furthermore, the apoptosis related proteins might be released from intermembrane space due to the destroyed mitochondria structure, which eventually induced the apoptosis of MCF-7 cells.

关 键 词：MCF-7细胞 细胞凋亡 细胞代谢组学 活性氧 线粒体跨膜电位 

分 类 号：R285[医药卫生—中药学] O657[医药卫生—中医学]