木香烃内酯对人乳腺癌MCF-7细胞生物学特性的影响及其机制  

Effects and mechanism of costunolide on biological characteristics of human breast cancer MCF-7 cells

作　　者：牛文意 王琦 张群 李贝 袁艳菊 谭睿[1] NIU Wenyi;WANG Qi;ZHANG Qun;LI Bei;YUAN Yanju;TAN Rui(College of Life Science and Engineering,Southwest Jiaotong University,Chengdu,Sichuan,610031 P.R.China)

机构地区：[1]西南交通大学生命科学与工程学院,四川成都610031

出　　处：《华西药学杂志》2023年第4期371-375,共5页West China Journal of Pharmaceutical Sciences

基　　金：国家自然科学基金资助项目(批准号:82074003);四川省重点研发项目(2020YFS0052);四川省政府应急重大专项(2021XYCZ008)。

摘　　要：目的探讨木香烃内酯(Cos)对人乳腺癌MCF-7细胞生物学特性的影响及其作用机制。方法体外培养MCF-7细胞,并用不同浓度Cos(0、5、10、20、40、80、120μmol·L^(-1))分别培养12、24、48 h,采用MTT法检测细胞抑制率。设空白组和Cos低、中、高剂量组(12.8、25.6、51.2μmol·L^(-1)),培养细胞24 h后,用流式细胞仪检测细胞周期及细胞凋亡情况;用Transwell法检测细胞的迁移能力;用蛋白印迹法检测生物学特性相关蛋白的表达。结果不同浓度Cos均可抑制MCF-7细胞的增殖,且不同时间的半数抑制浓度(IC50)分别为30.53、25.55、12.76μmol·L^(-1)。Cos可抑制S、G2/M期细胞,促进MCF-7细胞凋亡。与对照组比较,Cos显著抑制MCF-7细胞的迁移能力,明显下调Cyclin A、Cyclin B1、Bcl-2、MMP-2、MMP-9蛋白的表达,并上调Bax、p-JNK、Cleaved caspase-3、Cleaved caspase-9蛋白的表达。结论Cos通过抑制Cyclin A和Cyclin B1蛋白的表达来抑制MCF-7细胞的增殖,激活线粒体途径诱导其凋亡,并通过抑制MMP-2和MMP-9的表达来降低细胞迁移能力。OBJECTIVE To investigate the effect of costunolide(Cos)on the biological characteristics of human breast cancer cells(MCF-7)and its mechanism.METHODS MCF-7 cells were cultured in vitro and treated with different concentrations of Cos(0,5,10,20,40,80,120μmol·L^(-1))for 12,24,48 h,respectively.MTT assay was used to detect the cell inhibition rate.Blank group and Cos low,medium and high dose groups(12.8,25.6,51.2μmol·L^(-1))were set up.After 24 hours of culture,cell cycle and apoptosis were detected by flow cytometry.Transwell assay was used to detect migration ability.Western blotting was used to detect the expression of proteins related to biological characteristics.RESULTS Different concentrations of Cos could inhibit the proliferation of MCF-7 cells,and the IC50 values of different time points were 30.53,25.55,12.76μmol·L^(-1),respectively.Flow cytometry analysis showed that Cos inhibited cells in the S and G2/M phases and promoted the apoptosis of MCF-7 cells.Cos inhibited the migration ability of MCF-7 cells compared with the control group.In addition,Cos could significantly down-regulate the protein expression of Cyclin A,Cyclin B1,Bcl-2,MMP-2 and MMP-9,and up-regulate the protein expression of Bax,p-JNK,Cleaved caspase-3 and Cleaved caspase-9.CONCLUSION Cos can inhibit the proliferation of MCF-7 cells by inhibiting the expression of Cyclin A and Cyclin B1,induce apoptosis by activating mitochondrial pathway,and reduce the migration of MCF-7 cells by inhibiting the expression of MMP-2 and MMP-9.

关 键 词：木香烃内酯 乳腺癌 抗肿瘤 人乳腺癌细胞 细胞凋亡 细胞周期 细胞迁移 细胞增殖 

分 类 号：R96[医药卫生—药理学]