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基于网络药理学的慈丹胶囊抗肝癌作用机制探讨
辛宝,解方园,姚晨,张菁,黄婷婷,黄玉凤*
0
(海军军医大学(第二军医大学)第三附属医院药材科, 上海 200438
*通信作者)
摘要:
目的 构建慈丹胶囊活性成分-作用靶点网络和蛋白质-蛋白质相互作用(PPI)网络,对靶点涉及的功能和通路进行分析,探讨慈丹胶囊抗肝癌的作用机制。方法 通过中药系统药理学数据库与分析平台(TCMSP)挖掘慈丹胶囊中的主要活性成分。利用药物靶点分析平台(STITCH)、GeneCards数据库和在线人类孟德尔遗传数据系统(OMIM)预测和筛选慈丹胶囊活性成分对应靶点中与肝细胞癌相关的靶点。采用Cytoscape 3.8.2软件构建活性成分-作用靶点网络,采用String数据库和Cytoscape 3.8.2软件获得PPI网络。采用注视、可视化和集成发现数据库(DAVID)对靶点进行基因本体(GO)及京都基因与基因组百科全书(KEGG)富集分析。结果 筛选得到慈丹胶囊活性成分18个,共得到97个可能与肝细胞癌相关的作用靶点,活性成分-作用靶点网络分析显示慈丹胶囊具有多成分、多靶点的作用特点。构建的PPI网络涉及88个节点和467条边。GO富集分析结果表明,慈丹胶囊抗肝癌作用的靶点主要涉及细胞过程、生物调控、代谢过程、对化学刺激的反应等生物学过程。KEGG富集分析结果显示,慈丹胶囊抗肝癌作用的靶点主要涉及TNF、PI3K-AKT、MAPK等信号通路。结论 慈丹胶囊抗肝癌作用具有多成分、多靶点、多通路的特点,其可能通过调节TNF、PI3K-AKT、MAPK等信号通路发挥作用。
关键词:  慈丹胶囊  肝细胞癌  网络药理学  分子机制
DOI:10.16781/j.CN31-2187/R.20211320
投稿时间:2021-12-31修订日期:2022-04-15
基金项目:国家自然科学基金(81803450).
Effect of Cidan capsule on hepatocellular carcinoma: a mechanism study based on network pharmacology
XIN Bao,XIE Fang-yuan,YAO Chen,ZHANG Jing,HUANG Ting-ting,HUANG Yu-feng*
(Department of Pharmacy, The Third Affiliated Hospital of Naval Medical University (Second Military Medical University), Shanghai 200438, China
*Corresponding author)
Abstract:
Objective To construct an active component-target network and protein-protein interaction (PPI) network of Cidan capsule, analyze the functions and pathways involved in the targets, and explore the mechanism of Cidan capsule against liver cancer. Methods The main active components of Cidan capsule were mined through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The targets related to the treatment of hepatocellular carcinoma of the active components of Cidan capsule were predicted and screened by Search Tool for Interactions of Chemicals (STITCH), GeneCards, and Online Mendelian Inheritance in Man (OMIM). Cytoscape software was used to construct the active component-target network, and String database and Cytoscape software were used to construct the PPI network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using the Database for Annovation, Visualization, and Integrated Discovery (DAVID). Results Eighteen active components of Cidan capsule were screened, and a total of 97 targets related to hepatocellular carcinoma were obtained. The analysis of active component-target network showed that the effect of Cidan capsule was characterized by multiple components and multiple targets. The constructed PPI network involved 88 nodes and 467 edges. The results of GO enrichment analysis showed that cellular processes, biological regulation, metabolic process and response to chemical stimulation were mainly involved in the effect of Cidan capsule on hepatocellular carcinoma. The results of KEGG enrichment analysis showed that the targets of Cidan capsule for hepatocellular carcinoma were mainly involved in tumor necrosis factor (TNF), phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) and mitogen-activated protein kinase (MAPK) signaling pathways. Conclusion The effect of Cidan capsule on hepatocellular carcinoma is characterized by multiple components, multiple targets, and multiple pathways, and it may play a role by regulating TNF, PI3K-AKT and MAPK pathways.
Key words:  Cidan capsule  hepatocellular carcinoma  network pharmacology  molecular mechanism