Mechanism of Baitouweng Decoction in the Treatment of Colitis-Associated Colorectal Cancer：A Study Based on Network Pharmacology and Experimental Verification

OBJECTIVE To explore the pharmacodynamic material basis and mechanism of action of Baitouweng Decoction in the intervention of colitis-associated colorectal cancer (CAC), and to conduct preliminary verification through in vitro experiments. METHORDS　Active ingredients of Baitouweng Decoction were identified using the TCMSP, Traditional Chinese Medicine Integrated Database (TCMID), and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine (TCMIP) database combined with literature mining. The PharmMapper Server platform was used to predict the targets of these active ingredients. The relationship between the targets of Baitouweng Decoction and CAC was verified by cross-referencing them with disease targets from GeneCards and drug targets associated with CAC chemotherapy from DrugBank. Network models of “Traditional Chinese Medicine-Active Ingredient-Target” and “Active Ingredient-Target” were constructed using Cytoscape software. Signaling pathways involved in the intervention of CAC by Baitouweng Decoction were analyzed using the DAVID database. The proliferation and apoptosis of SW480 colon cancer cells treated with Baitouweng Decoction were assessed using the CCK-8 assay and flow cytometry; the expression of inflammatory factors was measured via qRT-PCR; and changes in key proteins within the EGFR and PI3K/AKT signaling pathways in SW480 cells were detected by Western blot.

RESULTS The “Active Ingredient-Target” network analysis identified 98 active ingredients and 87 targets (including 12 core active ingredients and 11 core targets). KEGG pathway analysis highlighted pathways related to cancer, prostate cancer, proteoglycans in cancer, the PI3K-AKT signaling pathway, and EGFR tyrosine kinase inhibitors. Molecular docking results demonstrated that compounds such as limonin, candletoxin A, and fraxin exhibited strong binding affinities with HRAS, IGF1, MAP2K1, and HSP90AA1. In vitro experiments confirmed that Baitouweng Decoction effectively inhibited the proliferation of SW480 cells and promoted apoptosis; simultaneously, it downregulated the expression of target proteins EGFR, p-AKT, and p-PI3K, and effectively suppressed the expression of IL-6, IL-1β, TNF-α, and iNOS.

CONCLUSION Baitouweng Decoction inhibits the progression of colitis-associated colorectal cancer and promotes tumor cell apoptosis through a multi-level, multi-pathway mechanism involving the modulation of EGFR and its downstream signaling pathways.