月见草素B通过调控P53抑制乳腺癌细胞的增殖和迁移  

Oenothein B inhibits proliferation and migration of breast cancer cells by regulating P53

作　　者：罗茂红 何娅 李红 陈腾祥 雷珊 张金娟 王璐 LUO Mao-hong;HE Ya;LI Hong;CHEN Teng-xiang;LEI Shan;ZHANG Jin-juan;WANG Lu(Department of Physiology,School of Basic Medical Sciences,Guizhou Medical University,Guiyang 550025,China;Functional Experimental Center,School of Basic Medical Sciences,Guizhou Medical University,Guiyang 550025,China)

机构地区：[1]贵州医科大学基础医学院生理学教研室,贵州贵阳550025 [2]贵州医科大学基础医学院机能学实验中心,贵州贵阳550025

出　　处：《中国中药杂志》2023年第14期3904-3912,共9页China Journal of Chinese Materia Medica

基　　金：贵州省科学技术厅项目(黔科合LH字[2016]7351);贵州省科技厅科学技术基金一般项目(黔科合基础[2020]1Y344)。

摘　　要：通过体外细胞培养、网络药理学和分子对接,研究月见草素B(oenothein B,OEB)对乳腺癌MCF-7、MDA-MB-231细胞增殖、凋亡、侵袭和迁移的影响及其作用机制。体外细胞实验发现OEB抑制乳腺癌细胞的增殖和克隆形成能力,并促进乳腺癌细胞的凋亡和凋亡小体的形成,同时OEB抑制乳腺癌细胞的侵袭和迁移。利用SwissTargetPrediction数据库获得OEB的靶点,在GeneCards数据库获得乳腺癌作用靶点,在Venny 2.1软件中分别录入OEB与乳腺癌的作用靶点,获得OEB与乳腺癌的共同作用靶点韦恩图。在STRING数据库中,输入OEB与乳腺癌共同靶点,构建蛋白-蛋白互作(PPI)网络,将PPI网络录入Cytoscape 3.7.2软件进行网络拓扑结构分析,根据蛋白关联强度筛选关键靶点,并对关键靶点进行KEGG通路富集分析;使用AutoDock软件对OEB和筛选的关键靶点进行分子对接验证,发现OEB与P53的活性口袋稳定结合,同时OEB促进P53蛋白的表达;沉默P53后MCF-7、MDA-MB-231细胞活力和迁移能力增加,加入OEB处理后逆转了这种变化。因此该研究表明OEB可抑制乳腺癌MCF-7、MDA-MB-231细胞的增殖、迁移和侵袭,并促进乳腺癌MCF-7、MDA-MB-231细胞凋亡,这可能与靶向调控P53有关。The effects of oenothein B(OEB)on the proliferation,apoptosis,invasion,and migration of breast cancer MCF-7 and MDA-MB-231 cells were investigated by cell culture in vitro,network pharmacology,and molecular docking.In vitro cell experiments revealed that OEB inhibited the proliferation and colony formation ability,and promoted the apoptosis and formation of apoptotic bodies in breast cancer cells,as well as inhibited the invasion and migration of breast cancer cells.The targets of OEB were obtained using SwissTargetPrediction database and breast cancer targets were obtained from GeneCards.The targets of OEB and breast cancer were entered separately in Venny 2.1 software to obtain the Venn diagram of common targets of OEB and breast cancer.The common targets of OEB and breast cancer were input into STRING database to construct a protein-protein interaction(PPI)network,which was entered into Cytoscape 3.7.2 software for network topology analysis.Key targets were screened according to protein association strength,and analyzed for KEGG pathway enrichment.Molecular docking of OEB to key targets using AutoDock software revealed that OEB stably bound to the active pocket of P53,while OEB promoted the expression of P53 protein.MCF-7 and MDA-MB-231 cell viability and migration ability increased after silencing P53,and this change was reversed after treatment with OEB.Therefore,this study showed that OEB inhibited the proliferation,migration,and invasion of breast cancer MCF-7 and MDA-MB-231 cells,and promoted the apoptosis of breast cancer MCF-7 and MDA-MB-231 cells,which may be related to the targeted regulation of P53.

关 键 词：乳腺癌细胞 月见草素B 增殖 凋亡 迁移 

分 类 号：R285[医药卫生—中药学]