Network Pharmacology and Molecular Docking Analyses of the Synergistic Mechanism of Babao Dan and Oxaliplatin in Colorectal Cancer

Abstract

<bold>Objective</bold> To further explore the mechanism of Babao Dan (BBD) combined with oxaliplatin (L-OHP) in treating colorectal cancer (CRC) through a network pharmacology analysis. <bold>Methods</bold> The analysis involved the following steps: screen the chemical components of BBD through literature review of Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Chemistry Database, PubChem, and other databases; obtain L-OHP-related targets through GeneCards database; and search CRC-related targets through OMIM, GeneMap, TTD, DisGeNET, CTD, GeneCards, and other databases. After the intersection and mapping of drugs and disease, the protein-protein interaction (PPI) network and core targets were obtained using STRING database and CytoScape software. MetaScape database was used to analyze the core targets to obtain GO biological processes and KEGG pathways. <bold>Results</bold> BBD contained 495 chemical components with 204 active components screened out through the Swiss ADME database and 770 targets were obtained through the Swiss Target Prediction database. After the intersection of BBD and 775 targets of L-OHP with the CRC targets, it resulted in 74 potential targets. Twenty-four core targets were determined from the 74 intersection targets, which were related to the positive regulation of kinase activity, the positive regulation of cell migration, and peptidyl-serine modification in GO biological process. The KEGG pathway analysis showed that the core targets were related to pathway in cancer, proteoglycan in cancer, endocrine resistance, and microRNA in cancer, TNF signaling pathway, platinum resistance, and other pathways. Molecular docking showed that the core targets could bind to the most examined compounds. <bold>Conclusion</bold> Quercetin-7-olate, cyclo (L-tyrosyl-L-phenylalanyl), panaxadiol, and other compounds in BBD may play an anti-colorectal cancer effect in multiple pathways, including EGFR, AKT1, mTOR, and other targets in synergy with L-OHP.