神经药理学报 ›› 2022, Vol. 12 ›› Issue (1): 1-10.DOI: 10.3969/j.issn.2095-1396.2022.01.001

• 研究论文 •    下一篇

基于网络药理探讨半夏对肝癌的作用机制

陈帆,任君旭,张静   

  1. 河北北方学院基础医学院,张家口,075000,中国
  • 出版日期:2022-02-26 发布日期:2023-08-30
  • 通讯作者: 任君旭,硕士生导师;E-mail:junxur12@163.com
  • 作者简介:陈帆,在读硕士研究生;E-mail:2301947835@qq.com

Prediction of the Action Mechanism of Pinellia on Liver Cancer Based on Network Pharmacology and Molecular Docking

CHEN Fan,REN Jun-xu,ZHANG Jing   

  1. School of Basic Medicine,Hebei North University,Zhangjiakou,075000,China
  • Online:2022-02-26 Published:2023-08-30

摘要:

目的:通过网络药理学和分子对接方法探讨半夏在肝癌中的抗肿瘤机制。方法:利用TCMSP 数据库 以生物利用度(oral bioavailability,OB)≥30%、类药指数(drug like index,DL)≥0.18 筛选出半夏的活性成分 及相对应的靶点,通过GeneCards、DisGeNET、TTD 和Drugbank 数据库以“liver cancer”为关键词检索相关靶 点;通过Venny 平台获取半夏和肝癌的交集靶点,STRING 软件建立PPI 网络图并用“Degree”、“Betweenness”、 “Closeness”选取关键靶点,交集靶点输入DAVID 平台获取信息,继而用微生信软件进行GO 功能富集和KEGG 通路富集分析;通过Autodock Tools 1.5.7 软件将核心靶点及共同对应的活性成分黄芩素进行分子对接。结果: 共筛选得到半夏13 个活性成分,相对应的靶点172 个、肝癌相关靶点1 227 个、半夏与肝癌的交集靶点31 个。 GO 功能富集分析得到343 个条目,包括生物过程条目258 个(如细胞对缺氧的反应、细胞凋亡过程的正向调 节、基因表达的负调控),细胞定位条目22 个(如核质、细胞质、线粒体、染色质),分子功能条目63 个(如转录共 激活因子结合、转录因子活性、序列特异性DNA 结合)。通过KEGG 通路注释得101 条信号通路,如癌症通路、 P53 信号通路、AGE-RAGE 信号通路、人巨细胞病毒感染通路等。分子对接结果显示,关键靶点TP53、AKT1、 VEGFA、HIFVA 与主要活性成分黄芩素有较好亲和力。结论:半夏治疗肝癌通过多成分、多靶点、多通路协同起 效,本研究为后续研究提供了充分的理论依据。

关键词: 半夏, 肝癌, 网络药理学, 分子对接, 作用机制

Abstract:

Objective:To investigate the anti-tumor mechanism of Pinellia sinensis in hepatocellular carcinoma(HCC) by network pharmacology and molecular docking methods. Methods:TCMSP database was used to screen the active ingredients and corresponding targets of Pinellia with bioavailability(OB)≥30% and drug-like index(DL)≥0.18. GeneCards, DisGeNET,TTD and Drugbank databases were searched with “liver cancer” as the key word. The intersection targets of Pinellia tuber and liver cancer were obtained through the Venny platform, and the PPI network was established by STRING software and the key targets were selected by “Degree”,“Betweenness” and “Closeness”. The intersection targets were input into the DAVID platform to obtain information. Then GO function enrichment and KEGG pathway enrichment analysis were performed by wechat software. Autodock Tools 1.5.7 software was used to perform molecular docking of the core targets and their corresponding active ingredient baicalein. Results:The results showed that a total of 13 active components of Pinellia were screened, corresponding to 172 targets. 1 227 targets related to liver cancer. There were 31 intersection targets between Pinellia and HCC. GO functional enrichment analysis yielded 343 items, including 258 biological process items(such as cell response to hypoxia,positive regulation of apoptosis process,and negative regulation of gene expression),22 cellular localization items(such as nucleoplasm,cytoplasm,mitochondria,and chromatin). There were 63 molecular function items (such as transcription coactivator binding,transcription factor activity,sequence specific DNA binding). Through KEGG pathway annotation,101 signaling pathways were identified,such as cancer pathway,P53 signaling pathway,AGE-RAGE signaling pathway,human cytomegalovirus infection pathway,etc. Molecular docking results showed that the key targets TP53,AKT1, VEGFA,and HIFVA had a good affinity with baicalein,the main active ingredient. Conclusion: Pinellia ternata has synergistic effect on liver cancer through multiple components,targets and pathways. This study provides sufficient theoretical basis for further research.

Key words: Pinellia hepatoma, liver cancer, network pharmacology, molecular docking, mechanism of action