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    谢玲, 益钧, 宋永佳, 李卓渝, 范立强, 赵黎明. 基于网络药理学探究EGCG干预MDA-MB-231细胞的潜在分子机制[J]. 华东理工大学学报(自然科学版), 2021, 47(6): 690-698. DOI: 10.14135/j.cnki.1006-3080.20201126003
    引用本文: 谢玲, 益钧, 宋永佳, 李卓渝, 范立强, 赵黎明. 基于网络药理学探究EGCG干预MDA-MB-231细胞的潜在分子机制[J]. 华东理工大学学报(自然科学版), 2021, 47(6): 690-698. DOI: 10.14135/j.cnki.1006-3080.20201126003
    XIE Ling, YI Jun, SONG Yongjia, LI Zhuoyu, FAN Liqiang, ZHAO Liming. Underlying Molecular Mechanism of EGCG Against MDA-MB-231 Cells Based on Network Pharmacology[J]. Journal of East China University of Science and Technology, 2021, 47(6): 690-698. DOI: 10.14135/j.cnki.1006-3080.20201126003
    Citation: XIE Ling, YI Jun, SONG Yongjia, LI Zhuoyu, FAN Liqiang, ZHAO Liming. Underlying Molecular Mechanism of EGCG Against MDA-MB-231 Cells Based on Network Pharmacology[J]. Journal of East China University of Science and Technology, 2021, 47(6): 690-698. DOI: 10.14135/j.cnki.1006-3080.20201126003

    基于网络药理学探究EGCG干预MDA-MB-231细胞的潜在分子机制

    Underlying Molecular Mechanism of EGCG Against MDA-MB-231 Cells Based on Network Pharmacology

    • 摘要: 基于网络药理学分析绿茶中的主要多酚物质表没食子儿茶素没食子酸酯 (Epigallocatechin Gallate, EGCG)对三阴性乳腺癌细胞MDA-MB-231的潜在作用靶点及其分子机理。使用数据库检索EGCG和MDA-MB-231的潜在靶点,两者的靶点基因相互映射取交集,获得共同作用靶点;借助软件Cytoscape 3.8.0绘制“靶点-通路”网络互作图、String数据库构建靶点蛋白的互作网络关系 (Protein-Protein Interaction,PPI),基于Metascape平台对靶点进行基因本体论 (Gene Ontology,GO) 和京都基因与基因组百科全书 (Kyoto Encyclopedia of Genes and Genomes,KEGG) 富集分析;通过分子对接和体外实验验证预测结果。结果表明:通过挖掘,共获得EGCG靶点537个,MDA-MB-231靶点181个,取交集获得88个共同潜在靶点,进一步筛选保留30个核心作用靶点;获得20条核心GO生物进程和17条KEGG信号通路,涉及到癌症信号通路,毒性耐受通路,胰腺癌通路、直肠癌通路,小细胞肺癌通路等;分子对接结果显示,EGCG可以通过非共价键与β-连环蛋白 (β-catenin) 结合;体外实验表明,肝细胞生长因子 (Hepatocyte Growth Factor,HGF) 能够诱导β-catenin的表达,而EGCG能够抑制HGF诱导的β-catenin的表达上调。EGCG可以通过多靶点、多途径干预MDA-MB-231,已经初步证实EGCG可以影响HGF/β-catenin途径。

       

      Abstract: To screen out the potential targets and molecular mechanisms of Epigallocatechin gallate (EGCG) in the treatment of triple negative breast cancer (MDA-MB-231). Databases were used to explore the potential targets between EGCG and MDA-MB-231. The “target-pathway” networks of common targets were constructed using Cytoscape 3.8.0 software, while the String database was used to draw and analyze the PPI network. Subsequently, the core genes were submitted to the Metascape database for GO and KEGG enrichment analyses, the prediction results were verified through in vitro experiment. A total of 537 EGCG targets and 181 disaster targets were obtained, 30 key targets were retained by further screening from 88 common potential targets. The results of the enrichment analyses showed that the active targets were involved in 20 core GO biological processes and 17 KEGG signaling pathways. such as cancer signaling pathways, toxic tolerance pathways, pancreatic cancer pathways, rectal cancer pathways, small cell lung cancer pathways. Molecular docking illuminated that EGCG could interact with β-catenin in a non-covalent manner. The in vitro experiment revealed that HGF could induce the expression of β-catenin, and EGCG could repress the HGF-induced over-expression of β-catenin. EGCG inhibited cell viability through multiple targets and multiple pathways, so it has been basically confirmed that EGCG can affect the HGF / β-catenin pathway, providing a theoretical and practical basis for further mechanism exploration.

       

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