Core target gene screening and mechanism analysis of yang-warming and toxin-resolving formula in treatment of colorectal cancer
Objective To identify the core target gene for yang-warming and toxin-resolving formula in treating colorectal cancer by network pharmacology and molecular docking,and to explore the mechanism of action.Methods The effective ingredients and related targets of yang-warming and toxin-resolving formula were screened out through TCMSP and Uniprot database.Colorectal cancer-related targets were obtained through the Genecards database.The intersection of these two datasets yielded potential targets for yang-warming and toxin-resolving formula in treating colorectal cancer.Based on STRING database and Cytoscape software,a protein-protein interaction(PPI)network was constructed,followed by topological analysis to identify the core target for yang-warming and toxin-resolving formula in treating colorectal cancer.Then Gene ontology(GO)function and KEGG pathway enrichment analysis were applied to the core target,and molecular docking was employed for structural validation of the key active ingredients shared by the six Chinese medicines and their core targets.Results By intersecting the 269 related targets of the six Chinese herbal medicines in yang-warming and toxin-resolving formula with the 1 349 colorectal cancer-related targets,we discovered 131 potential targets for treating colorectal cancer with yang-warming and toxin-resolving formula,and the topological analysis of the PPI network showed that there were 6 core targets,namely serine/threonine protein kinase 1(Akt1),p53,JUN,epidermal growth factor recep-tor(EGFR),estrogen receptor 1(ESR1),and tumor necrosis factor(TNF).The results from GO function and KEGG pathway enrichment analysis indicated that these core targets primarily acted on comprehensive tumor signaling pathways,cell senescence signaling pathways,p53 signaling pathways,TNF signaling pathways,and P13K/Akt signaling pathways,etc.Results from molecular docking demonstrated that low binding affinities were exhibited by Akt1,TNF,EGFR as well as the 11 key active ingredients of the six kinds of traditional Chinese medicines in the formula,among which,Worenine(methyl berberine)and TNF,and β-sitosterol and EGFR showed the lowest binding affinities,with values of-6.78 and-6.56,respectively.Conclusion The core target genes for treating colorectal cancer with yang-warming and toxin-re-solving formula include Akt1,p53,JUN,EGFR,ESR1,and TNF,and the mechanism may be related to the regulation of p53,TNF,P13K/Akt,and other signaling pathways.
yang-warming and toxin-resolving formulacolorectal carcinomanetwork pharmacologymolecular dockingcell proliferationapoptosisP13K/Akt signaling pathway
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