Icaritin suppresses colorectal cancer invasion and metastasis through regulation of epithelial-mesenchymal transition and the Wnt/β-catenin signaling pathway

BACKGROUND Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide, and treatment for advanced disease remains challenging. The natural compound icaritin has demonstrated anti-tumor properties, however its effects on CRC metastasis are not fully understood. AIM To investigate the inhibitory effects of icaritin on CRC and its underlying mechanism of action. METHODS The impact of icaritin on CRC cell invasion and migration was evaluated using in vitro and in vivo approaches. The viability of HCT116 and SW620 cells was assessed using the cell counting kit-8 assay. Epithelial-mesenchymal transition and Wnt/β-catenin signaling related proteins were analyzed by western blotting and immunofluorescence. Cell migration and invasion were evaluated using Transwell assays. Additionally, an orthotopic xenograft tumor model was established to provide further insights. RESULTS Icaritin significantly inhibited HCT116 and SW620 cell proliferation in a time-dependent manner and promoted apoptosis, as determined by flow cytometry analysis of apoptotic markers. It also suppressed cell migration and invasion. At the molecular level, icaritin downregulated the expression of N-cadherin, Snail, β-catenin, matrix metalloproteinase 2, and matrix metalloproteinase 9, while upregulating E-cadherin and adenomatous polyposis coli. In a mouse xenograft model, icaritin treatment significantly reduced tumor volume and weight compared to the control group. CONCLUSION Icaritin inhibits CRC cell invasion and metastasis by preventing epithelial-mesenchymal transition and suppressing the Wnt/β-catenin signaling pathway, highlighting its potential as a therapeutic agent for CRC.