基于网络药理学探究莪术油治疗胃癌的潜在活性成分及作用机制  

Potential bioactive components and mechanism of Zedoary Turmeric Oil in the treatment of gastric cancer based on network pharmacology

作　　者：陈倩莉 黎巍威[1] 叶晖[1] 张学智[1] CHEN Qianli;LI Weiwei;YE Hui;ZHANG Xuezhi(Department of Traditional Chinese Medicine and Integrated Chinese Medicine,Peking Universi-ty First Hospital,Institute of Integrative Medicine,Peking University,Beijing,100034,China)

机构地区：[1]北京大学第一医院中医中西医结合科北京大学中西医结合研究所,北京100034

出　　处：《中国中西医结合消化杂志》2021年第5期313-320,共8页Chinese Journal of Integrated Traditional and Western Medicine on Digestion

基　　金：国家自然科学基金面上项目(No:81973615)。

摘　　要：目的:基于网络药理学探讨莪术油治疗胃癌的潜在活性成分及相关分子机制。方法:查阅相关文献,通过中药系统药理学数据库与分析平台(TCMSP)、中药综合数据库(TCMID)及PubChem数据库检索莪术油的化学成分,并上传至Swiss Target Prediction平台获得潜在作用靶点;从GEO数据库获取GSE54129芯片数据,使用R语言获取胃癌组织与正常组织的差异表达基因;利用Cytoscape构建莪术油活性成分-靶点网络,采用Bisogenet构建莪术油治疗胃癌的蛋白质-蛋白质相互作用(PPI)网络,根据拓扑参数筛选关键网络;运用Metascape数据库对关键网络中的靶点进行基因本体(GO)富集分析和京都基因与基因组百科全书(KEGG)信号通路分析;最后,利用Cytohubba插件及拓扑分析筛选莪术油治疗胃癌的关键基因,并使用ONCOMINE数据库分析关键基因在胃癌中的表达情况。结果:从文献和数据库中获得莪术油30个化学成分,该成分对应的靶点共有487个,莪术醇、莪术二酮、新莪术二酮、莪术烯醇、异莪术烯醇、吉马酮为莪术油的主要作用成分;分析GSE54129芯片得到507个胃癌差异表达基因,与莪术油共有28个交集靶点;构建PPI网络并进一步筛选获得115个特征性靶点组成的关键网络;GO分析和KEGG信号通路分析表明,莪术油治疗胃癌主要参与了凋亡信号通路、PI3K-Akt信号通路、MAPK信号通路、Wnt信号通路、TGF-β信号通路等信号通路;并从关键网络中得到MCM2、ENO1、TP53、VCP等7个关键靶点,该关键基因在胃癌样本和正常样本中均存在显著表达差异。结论:该研究通过网络药理学结合生物信息学的方法初步预测了莪术油治疗胃癌的潜在活性成分、关键靶点和相关的信号通路,体现了莪术油治疗胃癌多成分、多靶点、多通路的整体协调作用,为后续进一步的基础实验与临床研究提供了理论依据。Objective: To explore the potential bioactive components and molecular mechanism of Zedoary Turmeric Oil against gastric cancer based on network pharmacology. Methods: The chemical compounds of Zedoary Turmeric Oil were screened by searching Traditional Chinese Medicine System Pharmacology Database(TCMSP), Traditional Chinese Medicine Integrated Database(TCMID) and PubChem database, and uploaded to the SwissTargetPrediction platform to obtain putative targets;we downloaded GSE54129 from GEO database to obtained differentially expressed genes(DEGs) between gastric cancer tissues and normal tissues;the compound-target network of Zedoary Turmeric Oil was constructed by Cytoscape, the protein-protein interaction(PPI) network and core network of Zedoary Turmeric Oil in treatment of gastric cancer were constructed by Bisogenet;gene ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed using Metascape platform;finally, Hub genes of Zedoary Turmeric Oil against gastric cancer were screened by Cytohubba, and expression of the hub genes in gastric cancer were analyzed using ONCOMINE database. Results: A total of 30 chemical compounds and 487 candidate targets of Zedoary Turmeric Oil were retrieved from literature and databases, curcumol, curdione, neocurdione, curcumenol, isocurcumenol and germacone were the main active components of Zedoary Turmeric Oil;we identified 507 DEGs from the data chip GSE54129 of gastric cancer expression profile, and there were 28 intersection targets with Zedoary Turmeric Oil;we constructed PPI network and further screened core network composed of 115 characteristic targets;GO and KEGG analysis were involved several signal pathways, such as apoptotic signaling pathway, PI3 K-Akt signaling pathway, MAPK signaling pathway, Wnt signaling pathway and TGF-β signaling pathway;7 Hub genes such as MCM2,ENO1,TP53,VCP were obtained from the core network, there were significant differences in the expressions of 7 Hub genes in gastric cancer sa

关 键 词：莪术油 胃癌 网络药理学 活性成分 分子机制 

分 类 号：R473[医药卫生—护理学]