Modulation of Wnt/β-Catenin Signaling Pathway by Bushenfang for Colorectal Tumor Inhibition in mice with Adenomatous Polyposis Coli Gene Mutation

Abstract

Colorectal cancer (CRC) remains a major health concern worldwide, with current treatments associated with significant side effects and resistance. Traditional Chinese medicine (TCM), particularly BuShenFang (BSF), has shown potential as an alternative therapeutic strategy. However, the exact mechanism of BSF's action in CRC treatment is not fully understood. Despite the promising anticancer properties of BSF, its mechanism in inhibiting colorectal tumor progression remains unclear, necessitating further investigation. This study aims to evaluate the inhibitory effects of BSF on intestinal adenoma development in APCmin/+ mice and elucidate its underlying mechanism, focusing on the Wnt/β-catenin signaling pathway. APCmin/+ mouse were randomly assigned into four groups: control, low-dose BSF (100 mg/kg), high-dose BSF (200 mg/kg), and xStAxVHLL (positive control). After 11 weeks of treatment, tumor burden, histopathological changes, cell proliferation, apoptosis, and key signaling proteins were assessed using HE staining, immunohistochemistry, TUNEL assay, and Western blot analysis. BSF treatment significantly reduced tumor count and size in a dose-dependent manner. High-dose BSF suppressed tumor cell proliferation, promoted apoptosis, and enhanced APC expression while inhibiting β-catenin accumulation and its downstream targets, including c-Myc, Cyclin D1, and COX-2. These findings suggest that BSF exerts its anti-tumor effects through modulation of the Wnt/β-catenin pathway. BSF demonstrates significant potential in inhibiting colorectal tumorigenesis via modulation of key oncogenic pathways. Further research is warranted to explore its clinical applications and optimize therapeutic dosing.