Ivermectin inhibits epithelial-to-mesenchymal transition via Wnt signaling in endocrine-resistant breast cancer cells

Abstract

Ivermectin (IVM), an antiparasitic drug, has been explored for its anticancer properties in various cancer types, including breast cancer. Endocrine therapy resistance poses a significant challenge in breast cancer treatment, often leading to metastasis prevention failure. This study aimed to investigate the effects of IVM on endocrineresistant breast cancer cells, focusing on mechanisms associated with epithelial-to-mesenchymal transition (EMT). IVM was administered to endocrine-resistant breast cancer cell lines, MCF-7/LCC2 (tamoxifen resistant) and MCF-7/ LCC9 (fulvestrant resistant), to evaluate its influence on cell proliferation, invasion, and EMT-related mechanisms. The findings indicated that IVM’s half-maximum inhibitory concentration (IC50) inhibited MCF-7/LCC2 and MCF-7/LCC9 at 9.35 and 9.06 µM, respectively, within 24h of treatment. Moreover, IC50 concentration treatment for 24h led to over a 50% reduction in cell motility and a 62% and 35% decrease in cell invasion in MCF-7/LCC2 and MCF-7/LCC9 cells, respectively. Metastasis biomarkers demonstrated that IVM treatment reduced the expression of vimentin and snail. The study also discovered that IVM diminished the expression of Wnt5a/b and lipoprotein receptor-related protein 6 (LRP6), associated with the metastasis-related Wnt signaling pathway. In conclusion, IVM inhibits the Wnt signaling pathway associated with EMT in the metastasis of endocrine-resistant breast cancer cells. These insights underscore the potential of repurposing IVM for endocrine-resistant breast cancer patients.