Molecular mechanism of Matrine Injection in treating colorectal cancer based on network pharmacology and molecular docking / 国际生物医学工程杂志

ABSTRACT

Objective:To explore the molecular mechanism of Matrine Injection in treating colorectal cancer based on network pharmacological analysis and molecular docking.Methods:Taking matrine as the object, the corresponding potential drug targets in matrine were obtained from Swiss Target Prediction database, and SuperPred database, and the database of traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP). Differential genes were obtained from gene expression omnibus (GEO), and GeneCards, OMIM, DrugBank, and CTD databases were used to collect colorectal cancer-related genes. Furthermore, core targets were screened by establishing protein-protein interaction (PPI) networks. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis were performed by bioconductor of R language. Finally, the molecular docking calculation was performed to evaluate the interaction between matrine and core targets.Results:Matrine contained 63 targets. A total of 14 198 targets for colorectal cancer were obtained. The topology analysis results of the PPI network showed that 5 main targets such as myelocytomatosis proteins (MYC), interleukin-6 (IL-6), Caspase-3 (CASP3), mammalian target of rapamycin (mTOR), and amphiregulin (AR). GO enrichment analysis found that biological process (BP) mainly includes hydrogen peroxide reaction, cell reaction to hydrogen peroxide and cell response to chemical stress, etc; Cell components (CC) mainly include lipid rafts, membrane microregions and synaptic membranes, etc; Molecular functions (MF) mainly include transcriptional coregulatory factor binding, postsynaptic neurotransmitter receptor activity and core promoter sequence-specific DNA binding. KEGG pathway analysis showed that it involved chemical carcinogenesis-receptor activation, tumor necrosis factor (TNF) signaling pathway, and Toll-like receptor signaling pathway, etc. Molecular docking showed that matrine had good binding with the core target.Conclusions:Matrine acts on targets such as MYC, IL-6, CASP3, mTOR, and AR, and exerts therapeutic effects on colorectal cancer by regulating chemical carcinogenesis-receptor activation, TNF signaling pathway, Toll-like receptor signaling, etc.