Network Pharmacology and Molecular Docking Elucidate the Mechanism of Phillyrin in Colorectal Cancer

Phillyrin is an important active component of the traditional Chinese medicinal herb <i>Forsythia suspensa</i> Vahl (Oleaceae) and has demonstrated anti-inflammatory, antioxidant, and antitumor properties. However, there is a paucity of studies investigating its therapeutic efficacy in colorectal cancer (CRC). Our research aims to explore the potential therapeutic effects and underlying mechanisms of phillyrin in treating CRC. Phillyrin potential targets were predicted using the ChEMBL, HERB, and SwissTargetPrediction databases. TCGA and GEO databases were employed to acquire targets associated with CRC. Afterward, we used the STRING web database to perform network analysis of protein-protein interactions (PPI) on the shared genes. Key genes were discovered in the PPI network and subsequently analyzed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Apoptosis analysis in colorectal cancer cells treated with varying amounts of phillyrin was conducted using flow cytometry. Additionally, western blot analysis was applied to assess the expression of PI3K/AKT signaling proteins, confirming the findings of the network pharmacology study. A total of 250 phillyrin target genes and 4414 CRC-related targets were screened. Eight central genes were obtained through PPI network topological analysis. Analysis of GO and KEGG enrichment indicated that phillyrin is strongly linked to various signaling pathways, particularly the PI3K/AKT pathway. In vitro experiments, treatment with phillyrin at a concentration of 0.2 mM induced apoptosis rates of approximately 17% in HT29 cells and 21.1% in HCT116 cells. Cell migration was also significantly inhibited, with HT29 migration reduced to about 15.7% and HCT116 migration reduced to about 33.4% of the control after 24 h of treatment. Additional examination indicated that the PI3K/AKT/mTOR pathway plays a vital role in determining the effectiveness and outlook of phillyrin treatment in colorectal cancer. This study reveals that phillyrin inhibits CRC cell metastasis and induces apoptosis via the PI3K/AKT/mTOR pathway, highlighting its promise as a potential therapeutic candidate for future colorectal cancer treatment.