Exploration of the potential molecular mechanism of magnolol in colorectal cancer treatment based on network pharmacology and molecular docking

Colorectal cancer (CRC) has experienced a global rise in incidence, with chemotherapy resistance becoming a significant challenge during clinical treatment. Magnolol, a natural compound derived from Chinese herbal medicine, has been shown to induce apoptosis in various cancer cell types. However, the identification of comprehensive therapeutic targets and the underlying mechanisms through which magnolol exerts its effects against CRC remain limited. Network pharmacology was employed to forecast drug targets and disease targets. The binding ability between magnolol and the central therapeutic target Cyclin-dependent kinase 4 (CDK4) was verified by molecular docking technology. Cell viability was detected by Cell Counting Kit-8 (CCK-8) assay. RT-qPCR and western blotting were applied to evaluate mRNA and protein expression, respectively. The detection of cell proliferation was carried out by means of colony formation. Cell migration was examined by wound healing assay. Transwell was employed to assess cell invasion. CCK-8 assay was conducted to evaluate the Half maximal inhibitory concentration (IC50) value of 5-Fluorouracil (5-FU) in DLD1 and SW620 cells. The binding affinity between forkhead box protein A 2 (FOXA2) and CDK4 was validated with Chromatin Immunoprecipitation (ChIP) and dual-luciferase reporter gene assay. A mouse xenograft model was established for the purpose of analysis in vivo . CDK4 was a potential target for magnolol in the treatment of CRC. Magnolol suppressed the expression of CDK4. Magnolol targeted CDK4 and inhibited CRC cell migration, invasion, and 5-FU resistance. Magnolol influenced CDK4 expression by regulating FOXA2. Magnolol modulated CRC cell function via the FOXA2/CDK4 pathway. Magnolol restrained CRC tumor growth by reducing FOXA2 expression. Magnolol inhibited the malignant progression and 5-FU resistance of CRC by targeting the FOXA2/CDK4 axis.