Ficus pandurata Hance suppresses colorectal cancer by targeting PI3K/Akt/mTOR pathway: A network pharmacology-guided experimental validation

Background: Ficus pandurata Hance (FPH), a traditional Chinese medicinal herb, is known for its antioxidant and anti-inflammatory activities. While its efficacy against ulcerative colitis has been reported, its potential role in colorectal cancer (CRC) remains under explored. This study aimed to investigate the anti-CRC activity of FPH decoction (FPHD), focusing on its molecular targets and underlying mechanisms through an integrated approach of network pharmacology, molecular docking, and experimental validation. Methods: The cytotoxicity of FPHD was assessed in CT-26 colorectal cancer cells and IEC-6 normal intestinal cells using the MTT assay. Anti-tumor efficacy was validated in a CT-26 tumor-bearing mouse model. Fifty-one bioactive compounds from FPHD were retrieved from prior UPLC-HRMS study. Potential targets were predicted via Swiss Target Prediction and PharmMapper, and intersected with CRC-related targets obtained from GeneCards, DisGeNET, Drug Bank, OMIM, and TTD databases. Network analysis, protein–protein interaction mapping, GO and KEGG enrichment, and molecular docking were conducted to identify core targets and pathways. Key findings were validated through Western Blot, ATP quantification, and flow cytometry. Results: FPHD selectively suppressed CT-26 cell viability without harming IEC-6 cells and significantly reduced tumor volume in vivo. Network pharmacology identified 216 overlapping targets between FPHD and CRC, with enrichment pointing to the PI3K/Akt/mTOR pathway. Docking results showed strong binding affinity between major FPHD compounds and Akt1. Mechanistically, FPHD downregulated p-Akt and p-mTOR while upregulating LKB1 and p-AMPK, leading to reduced ATP production and caspase-dependent apoptosis in CRC cells. Conclusion: This study reveals that FPHD exerts potent anti-tumor effects through modulation of the PI3K/Akt/mTOR axis, energy depletion, and apoptosis induction. These findings provide compelling evidence for the development of Ficus pandurataas a multi-target complementary therapeutic candidate for colorectal cancer management.