Resveratrol Prevents Breast Cancer Metastasis by Inhibiting Wnt/β-Catenin Pathway-Mediated Epithelial–Mesenchymal Transition

Background: Breast cancer is the most prevalent cancer in women, and metastatic breast cancer remains a major cause of cancer-related deaths. Resveratrol (RSV) is a natural compound found in various plants and is known to exhibit various anti-cancer effects. The present study aims to investigate the therapeutic effects and mechanisms of RSV in inhibiting breast cancer metastasis in a murine model of 4T1 breast tumor that shares close molecular features with human triple negative breast cancer. Methods: Murine breast cancer 4T1 cells were used to examine the effects of RSV on breast cancer metastasis and epithelial–mesenchymal transition (EMT). In vitro cell proliferation and Transwell migration assays and in vivo 4T1 tumor transplantation models were established in female Balb/c mice to determine the anti-metastatic effects of RSV and its mechanism of action. Results: RSV significantly inhibited 4T1 tumor cell migration and significantly decreased expression levels of EMT markers Snail and Vimentin, as well as the nuclear translocation of β-catenin both in vitro and in vivo. Knockdown of β-catenin similarly reduced the expression levels of EMT markers. RSV significantly decreased the number of lung metastases in 4T1-implanted mice by inhibiting Wnt/β-catenin signaling pathway activation. RSV (150 mg/kg/day) reduced the number of visible tumor metastatic nodules and the histological count of metastatic lung carcinomas by 51.82% and 62.58%, respectively, compared to vehicle administration. Conclusions: Our study provides important new mechanistic insight into the strong anti-cancer effects of RSV in inhibiting 4T1 breast cancer metastasis by preventing Wnt/β-catenin signaling pathway-mediated epithelial–mesenchymal transition. These findings suggest the therapeutic potential of RSV as a promising drug in the treatment of metastatic breast cancer.