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基于网络药理学探究EGCG干预MDA-MB-231细胞的潜在分子机制

谢玲 益钧 宋永佳 李卓渝 范立强 赵黎明

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). 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). doi: 10.14135/j.cnki.1006-3080.20201126003
XIE Ling, YI Jun, SONG Yongjia, LI Zhuoyu, FAN Liqiang, ZHAO Liming. Exploration of the Mechanism of EGCG Against MDA-MB-231 cells based on Network Pharmacology[J]. Journal of East China University of Science and Technology. doi: 10.14135/j.cnki.1006-3080.20201126003
Citation: XIE Ling, YI Jun, SONG Yongjia, LI Zhuoyu, FAN Liqiang, ZHAO Liming. Exploration of the Mechanism of EGCG Against MDA-MB-231 cells based on Network Pharmacology[J]. Journal of East China University of Science and Technology. 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

doi: 10.14135/j.cnki.1006-3080.20201126003
详细信息
    作者简介:

    谢玲(1994—),女,四川人,硕士生,主要研究方向:乳腺癌的治疗。E-mail:929045161@qq.com

    通讯作者:

    范立强,E-mail:liqiangfan@163.com

    赵黎明,E-mail:zhaoliming@ecust.edu.cn

  • 中图分类号: TS201.1

Exploration of the 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Cytoscape 3.8.0软件绘制“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,其中,已经初步证实EGCG可以影响HGF/β-catenin途径,为进一步机理探究提供理论和实践基础。

     

  • 图  1  EGCG和MDA-MB-231共同潜在靶点筛选

    Figure  1.  Screening of common and potential targets for EGCG and MDA-MB-231

    图  2  核心靶点网络互作图

    Figure  2.  Network interaction of core targets

    图  3  核心靶点的GO (A) 和KEGG (B) 分析

    Figure  3.  GO (A) and KEGG (B) analysis of core targets

    图  4  核心靶点-信号通路互作图

    Figure  4.  The interactions between core targets and pathways

    图  5  核心聚类模块

    Figure  5.  Core clustering modules

    图  6  EGCG与β-catenin的分子对接图

    Figure  6.  Moleculer Docking of EGCG to β-catenin

    图  7  Western Blot 检测β-catenin蛋白的表达

    Figure  7.  The expression of β-catenin identified by Western Blot analysis

    表  1  EGCG和MDA-MB-231共同潜在靶点

    Table  1.   Common and potential targets for EGCG and MDA-MB-231

    GeneProtein name
    MAPK14Mitogen-activated protein kinase 14
    AKT1RAC-alpha serine/threonine-protein kinase
    MAPK3Mitogen-activated protein kinase 3
    SP1Transcription factor Sp1
    MAPK8Mitogen-activated protein kinase 8
    SRCProto-oncogene tyrosine-protein kinase Src
    IGF1Insulin-like growth factor I
    VEGFAVascular endothelial growth factor A
    METHepatocyte growth factor receptor
    JUNTranscription factor AP-1
    HGFHepatocyte growth factor
    SMAD3Mothers against decapentaplegic homolog 3
    FOSProto-oncogene c-Fos
    RB1Retinoblastoma-associated protein
    ITGB1Integrin beta-1
    PTK2Focal adhesion kinase 1
    RELATranscription factor p65
    PIK3CAPhosphatidylinositol 3-kinase catalytic subunit alpha isoform
    BCL2L1Bcl-2-like protein 1
    STAT3Signal transducer and activator of transcription 3
    ESR1Estrogen receptor
    NFKB1Nuclear factor NF-kappa-B p105 subunit
    MAPK1Mitogen-activated protein kinase 1
    CDKN1ACyclin-dependent kinase inhibitor 1
    EGFREpidermal growth factor receptor
    EGFEpidermal growth factor
    CTNNB1Catenin beta-1
    BCL2Apoptosis regulator Bcl-2
    CDH1Cadherin-1
    TP53Cellular tumor antigen p53
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出版历程
  • 收稿日期:  2020-11-26
  • 网络出版日期:  2021-03-31

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