穿心莲内酯对人乳腺癌细胞迁移和侵袭的抑制作用  

Inhibitory effect of Andrographolide on the metastasis and invasion of human breast cancer cells

作　　者：傅鹤秀 鹿蓓蓓 陈秋云[2] 高静[1] FU Hexiu;LU Beibei;CHEN Qiuyun;GAO Jing(School of Pharmacy,Jiangsu University,Zhenjiang Jiangsu 212013,China;School of Chemistry and Chemical Engineering,Jiangsu University,Zhenjiang Jiangsu 212013,China)

机构地区：[1]江苏大学药学院,江苏镇江212013 [2]江苏大学化学化工学院,江苏镇江212013

出　　处：《江苏大学学报（医学版）》2022年第1期32-37,共6页Journal of Jiangsu University：Medicine Edition

基　　金：国家自然科学基金资助项目(81373400)。

摘　　要：目的:探究穿心莲内酯对人乳腺癌MDA-MB-231细胞迁移和侵袭的抑制作用及机制。方法:用穿心莲内酯0,5,10,20,40和80μmol/L处理MDA-MB-231细胞24 h,MTT法检测细胞存活率;伤口愈合和Transwell小室实验检测细胞迁移与侵袭能力;逆转录聚合酶链反应检测解偶联蛋白2(uncoupling protein-2,UCP2)mRNA表达;蛋白质印迹法检测UCP2和丙酮酸脱氢酶(pyruvate dehydrogenase,PDH)蛋白表达水平;乳酸试剂盒检测乳酸含量;JC-1染色后共聚焦显微镜检测线粒体膜电位。结果:穿心莲内酯对MDA-MB-231细胞增殖的抑制作用具有浓度依赖性;与0μmol/L组相比,10,20,40μmol/L组MDA-MB-231细胞的迁移与侵袭能力受到抑制(P<0.05或P<0.01);UCP2的mRNA和蛋白表达下调(P<0.05或P<0.01),线粒体膜电位升高,PDH蛋白表达上调,细胞内乳酸含量下降(P<0.05或P<0.01)。结论:穿心莲内酯可能通过抑制乳腺癌的糖酵解和改变能量代谢的方式抑制MDA-MB-231细胞的迁移与侵袭,其机制可能与UCP2有关。Objective:To investigate the effect and mechanism of Andrographolide(Andro)on the metastasis and invasion of human breast cancer MDA-MB-231 cells.Methods:MDA-MB-231 cells were treated with Andro(0,5,10,20,40 and 80μmol/L)for 24 h.MTT assay was used to detect cell proliferation.Wound healing and Transwell experiment were applied to detect cell migration and invasion ability.Reverse transcription polymerase chain reaction were applied to detect uncoupling protein 2(UCP2)mRNA expression.The protein expressions of UCP2 and pyruvate dehydrogenase(PDH)were detected by Western blotting.Lactic acid kit was used to detect lactic acid content.JC-1 staining and laser confocal microscope were used to detect mitochondrial membrane potential(MMP).Results:Compared with the control group,Andro significantly inhibited the proliferation of MDA-MB-231 cells in a concentration-dependent manner.Compared with 0μmol/L,the metastasis and invasion of MDA-MB-231 cells in the 10,20,and 40μmol/L groups were inhibited(P<0.05 or P<0.01);UCP2 mRNA and protein expression were down-regulated(P<0.05 or P<0.01),MMP was increased,PDH protein expression was up-regulated,and intracellular lactate content was decreased(P<0.05 or P<0.01).Conclusion:Andro may inhibit the metastasis and invasion of MDA-MB-231 cells by inhibiting the glycolysis of breast cancer cells and altering energy metabolism,which may be related to inhibition of UCP2.

关 键 词：穿心莲内酯 乳腺癌 MDA-MB-231细胞 迁移 侵袭 解偶联蛋白-2 

分 类 号：R285[医药卫生—中药学]