A Study on the Mechanism of Herbal Drug FDY003 for Colorectal Cancer Treatment by Employing Network Pharmacology

Abstract

Colorectal cancer (CRC) originates from the uncontrolled growth of epithelial cells in the colon or rectum. Annually, 1.9 million new CRC cases are being reported, causing 0.9 million deaths worldwide. The suppressive effects of the herbal prescription FDY003, a mixture of Cordyceps militaris, Lonicera japonica Thunberg, and Artemisia capillaris Thunberg, against CRC have previously been reported. Nonetheless, the multiple compound-multiple target mechanisms of FDY003 in CRC cells have not been fully elucidated. In this study, we used network pharmacology (NP) to analyze the polypharmacological mechanisms of action of FDY003 in CRC treatment. FDY003 promoted the suppression of viability of CRC cells and strengthened their sensitivity to anticancer drugs. The NP study enabled the investigation of 17 pharmaceutical compounds and 90 CRC-related genes that were targets of the compounds. The gene ontology terms enriched with the CRC-related target genes of FDY003 were those involved in the control of a variety of phenotypes of CRC cells, for instance, the decision of apoptosis and survival, growth, stress response, and chemical response of cells. In addition, the targeted genes of FDY003 were further enriched in various Kyoto Encyclopedia of Genes and Genomes pathways that coordinate crucial pathological processes of CRC; these are ErbB, focal adhesion, HIF-1, IL-17, MAPK, PD-L1/PD-1, PI3K-Akt, Ras, TNF, and VEGF pathways. The overall analysis results obtained from the NP methodology support the multiple-compound-multiple-target-multiple-pathway pharmacological features of FDY003 as a potential agent for CRC treatment.