摘要
目的通过网络药理学方法预测四君子汤治疗结直肠癌潜在的作用靶点及信号通路。方法利用TCMSP获得四君子汤的化学成分及作用靶点,结合Swiss Target Prediction网站进行靶标垂钓;通过TTD、OMIM、Drugbank和GeneCards数据库收集结直肠癌相关靶点。运用Venn图取药物和疾病交集靶点,并在Unitprot数据库查询靶标蛋白基因名,通过STRING在线数据库对二者交集的靶点蛋白构建蛋白相互作用网络(PPI),采用Cytoscape 3.7.1软件进行可视化处理。使用David网站进行GO功能富集分析和KEGG通路富集分析。结果获得四君子汤的有效成分134个,PPI包含125个靶点蛋白,关键蛋白包括TP53、AKT1、IL6等。经GO富集分析得到四君子汤治疗结直肠癌主要通过516个生物学过程,53个细胞组成和98个分子功能发挥作用。KEGG通路富集结果显示,四君子汤治疗结直肠癌的机制可能与PI3K-Akt信号通路、TNF信号通路、FoxO信号通路等相关。结论四君子汤主要通过调节TP53、AKT1、IL-6等关键蛋白,干预PI3K-Akt、TNF、FoxO等信号通路来治疗结直肠癌,体现了四君子汤治疗结直肠癌“中药多成分-多靶标-多通路”的特点。
Objective To explore the potential target and signaling pathway of Sijunzi Decoction in treating Colorectal Cancer(CRC)with network pharmacology.Methods The Traditional Chinese Medicine System Platform(TCMSP)and Swiss Target Prediction database were adopted to establish the database of Sijunzi Decoction effective ingredients and targets.Therapeutic Target Database(TTD),Online Mendelian Inheritance in Man,Drugbank and GeneCards were used to build the CRC target database.The common gene names of target proteins were checked in Uniprot database.The STRING database was applied to analyze the interactions between the targets and the DAVID was used for the enrichment analysis on gene ontology(GO)biological process and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway.The network topology results were analyzed by Cytoscape 3.7.1 software.Results 134 active compounds of Sijunzi Decoction were gained,and PPI includes 125 targets protein(TP53,AKT1,IL-6,et al.).The 516 cellular biological processes,53 cellular component and 98 molecular function were obtained through GO biological process enrichment analysis.The result of KEGG pathway enrichment showed that PI3K-Akt signaling pathway,TNF signaling pathway and FoxO signaling pathway were the main pathways.Conclusion Sijunzi Decoction is mainly used to treat CRC by regulating key proteins such as TP53,AKT1,IL-6 and interfering with signal pathways such as PI3K-Akt,TNF and FoxO,reflecting the characteristics of Sijunzi Decoction in the treatment of CRC with multi-component,multi-target and multi-pathway characters.
作者
唐末
杨宇飞
宋卓
闫蕴孜
何斌
Tang Mo;Yang Yufei;Song Zhuo;Yan Yunzi;He Bin(Oncology Department,Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100091,China;Xiyuan Clinical Medical College,Beijing University of Chinese Medicine,Beijing 100029,China)
出处
《国际中医中药杂志》
2022年第2期206-211,共6页
International Journal of Traditional Chinese Medicine
基金
国家中医药管理局重大疑难疾病中西医临床协作结直肠癌项目[中国中医药办医政函(2018)275]。
关键词
四君子汤
结直肠肿瘤
网络药理学
成分-靶标-通路
Si Jun Zi Tang
Colorectal neoplasms
Network pharmacology
Ingredient-target-pathway
