ABSTRACT
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.
ABSTRACT
Objective:Based on the network pharmacology, this study preliminarily aims to explore the mechanism of Sijunzi Decoction in the intervention of colorectal cancer. Methods:The active components and targets of Sijunzi Decoction were gained by Traditional Chinese Medicine Pharmacology Database Systems (TCMSP); and the targets were standardized with the help of Uniprot database. The related targets of colorectal cancer were obtained by GeneCards database and Disgenet database, and the intersection targets of berbal medicine and diseases were screened by R language. The visual regulation network of "active ingredient-disease target" of Sijunzi Decoction was constructed by Cytoscape software, and the protein interaction network was constructed by STRING database. The functional enrichment analysis of gene ontology (GO) and the pathway enrichment analysis of Kyoto Encyclopedia of Gene and Genome (KEGG) were carried out by Bioconductor platform. Results:A total of 135 active components and 68 intersection targets of Sijunzi Decoction were obtained. The core target proteins included IL6, VEGFA, CASP3, EGFR and so on. GO functional enrichment analysis involved 91 items, which mainly affected transcription factor activity, enzyme activity, receptor activity and biochemical process regulation. KEGG pathway enrichment analysis contained 126 items, concerning infection, cancer, apoptosis, inflammation and other pathways. Conclusion:The active components of Sijunzi Decoction mainly regulate biological processes such as transcription factor activity and enzyme activity of colorectal cancer cells through cancer signal pathway and inflammatory signal pathway, so as to play a role of interventing of colorectal cancer.