Characterizing the Antitumor Effect of Coptis chinensis and Mume Fructus against Colorectal Cancer Based on Pharmacological Analysis

Abstract

Colorectal cancer (CRC) is the third most diagnosed cancer worldwide and is a significant cause of cancer-related deaths. Previous studies have observed that Coptis chinensis (CC) and Mume Fructus (MF) are effective against CRC, enteritis, and intestinal dysbiosis, but the chemical and pharmacological mechanisms remain poorly understood. In this study, we employed pharmacological network analysis to reveal mechanisms underlying the therapeutic effect of CC and MF against CRC. All compounds and targeted genes were obtained from the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP). Differentially expressed genes (DEGs) were identified based on GSE146587, GSE156720, and GSE184093 datasets. A protein-protein interaction (PPI) network was constructed to identify putative target genes of CC and MF. Ten key targeted genes were identified, including CCND1, ICAM1, IL1B, IL-6, MMP1, MMP3, MMP9, MYC, SERPINE1, and VEGFA. Among these genes, six (ICAM1, IL1B, IL-6, MMP1, MMP3, MMP9, and SERPINE1) were positively correlated with levels of effector memory CD4 T cells and natural killer T cells, and three (CCND1, MYC, and VEGFA) were negatively correlated with type 17 T helper cells and CD56dim natural killer cells. Molecular docking analysis showed that four compounds of CC and MF (kaempferol, oleanolic acid, quercetin, and ursolic acid) could affect CRC by interacting with target genes. Our study proved that pharmacological analysis could reliably assess the mechanism of traditional Chinese medicines for treating cancer.