| 摘要: |
| 目的：采用网络药理学和分子对接技术相结合的方法探究柯里拉京（Cor）治疗卵巢癌的关键作用靶点和分子机制。方法：利用PharmMapper、TargetNet及Swiss Target Prediction在线工具预测Cor的作用靶点，通过OMIM、TTD、CTD、DisGenet、PharmGKB及MalaCards数据库获取卵巢癌相关的疾病靶点，并将药物靶点与疾病靶点取交集得到Cor治疗卵巢癌的预测靶点。借助STRING数据库、Cytoscape 软件构建蛋白质-蛋白质相互作用（PPI）网络，并采用CentiScape插件筛选出PPI网络中的核心靶点。运用GEPIA和Kaplan-Meier Plotter在线平台分别对这些核心靶点进行基因表达差异分析和生存分析，以明确Cor治疗卵巢癌的关键靶点。利用DAVID数据库进行基因本体（GO）功能及京都基因与基因组百科全书（KEGG）通路富集分析。运用Autodock Vina软件进行正向分子对接，预测关键靶点和Cor之间的结合活性。结果：Cor治疗卵巢癌的预测作用靶点共24个，其中RAC-α丝氨酸/苏氨酸蛋白激酶(AKT1)、表皮生长因子受体(EGFR)、雌激素受体1(ESR1)、原癌基因酪氨酸蛋白激酶(SRC)是Cor治疗卵巢癌的关键靶点，主要涉及血管内皮生长因子(VEGF)信号通路、缺氧诱导因子-1(HIF-1)信号通路及叉头样转录因子(FoxO)信号通路，可能通过调控细胞凋亡、细胞增殖、血管内皮细胞迁移等生物过程而发挥治疗卵巢癌的作用。分子对接结果显示，Cor与预测靶点之间具有较好的亲和力，表明通过网络药理学预测作用靶点的方法具有良好的可靠性。结论：Cor是通过多靶点、多通路的协同作用来干预多个生物过程，从而发挥其抗卵巢癌疗效，为进一步研究其治疗卵巢癌的分子机制提供了新的线索。 |
| 关键词: 卵巢癌 柯里拉京 关键靶点 网络药理学 分子机制 |
| DOI： |
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| Key targets and molecular mechanism of corilagin in treatment of ovarian cancer：A study based on network pharmacology and molecular docking |
| LUO Guangwen,HUANG Lili,HUANG Xie |
| (Jinhua Hospital Affiliated to Zhejiang University School of Medicine，Jinhua 321000，Zhejiang，China;Ningbo Medical Center Lihuili Hospital，Ningbo 315040，Zhejiang，China;School of Military Preventive Medicine，Army Medical University，Chongqing 400038，China) |
| Abstract: |
| Objective：To investigate the key action targets and molecular mechanism of corilagin (Cor) in the treatment of ovarian cancer based on network pharmacology and molecular docking. Methods：PharmMapper，TargetNet，and Swiss Target Prediction online tools were used to predict the action targets of Cor，and OMIM，TTD，CTD，DisGenet，PharmGKB，and MalaCards databases were used to obtain the disease targets of ovarian cancer. The drug targets and the disease targets were intersected to obtain the predictive targets of Cor in the treatment of ovarian cancer. STRING database and Cytoscape software were used to establish a protein-protein interaction (PPI) network，and CentiScape plug-in was used to screen for the core targets in the PPI network. GEPIA and Kaplan-Meier Plotter online platform were used to perform a differential gene expression analysis and a survival analysis of these core targets to clarify the key targets of Cor in the treatment in ovarian cancer. DAVID database was used to perform the gene ontology functional enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Autodock Vina software was used to perform forward molecular docking to predict the binding activity between the key targets and Cor. Results：There were 24 targets for predicting the role of Cor in the treatment of ovarian cancer，among which RAC-alpha serine/threonine-protein kinase，epidermal growth factor receptor，estrogen receptor 1，and proto-oncogene tyrosine-protein kinase Src were the key targets for Cor in the treatment of ovarian cancer. The main signaling pathways involved included the vascular endothelial growth factor signaling pathway，the hypoxia-inducible factor-1 signaling pathway，and the forkhead transcription factor signaling pathway，and Cor might exert a therapeutic effect on ovarian cancer by regulating the biological processes such as cell apoptosis，cell proliferation，and vascular endothelial cell migration. Molecular docking showed relatively good binding activity between Cor and the predictive targets，suggesting that network pharmacology had good reliability in predicting action targets. Conclusion：Cor intervenes in multiple biological processes through the synergistic effect of multiple targets and pathways，thereby exerting a therapeutic effect on ovarian cancer，which provides new clues for further research on the molecular mechanism of Cor in the treatment of ovarian cancer. |
| Key words: ovarian cancer corilagin key targets network pharmacology molecular mechanism |
