Rujimongkon Kitiya, Adchariyasakulchai Patthamapon, Meeprasertskul Phum, Ketchart Wannarasmi
Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
PLoS One. 2025 Jun 26;20(6):e0326742. doi: 10.1371/journal.pone.0326742. eCollection 2025.
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 endocrine-resistant 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 24 h of treatment. Moreover, IC50 concentration treatment for 24 h 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.
伊维菌素（IVM）是一种抗寄生虫药物，其抗癌特性已在包括乳腺癌在内的多种癌症类型中得到研究。内分泌治疗耐药性是乳腺癌治疗中的一个重大挑战，常常导致预防转移失败。本研究旨在探讨IVM对内分泌耐药乳腺癌细胞的影响，重点关注与上皮-间质转化（EMT）相关的机制。将IVM应用于内分泌耐药乳腺癌细胞系MCF-7/LCC2（他莫昔芬耐药）和MCF-7/LCC9（氟维司群耐药），以评估其对细胞增殖、侵袭及EMT相关机制的影响。研究结果表明，在治疗24小时内，IVM的半数最大抑制浓度（IC50）分别在9.35和9.06 μM时抑制MCF-7/LCC2和MCF-7/LCC9。此外，IC50浓度处理24小时导致MCF-7/LCC2和MCF-7/LCC9细胞的细胞运动性分别降低超过50%，细胞侵袭分别减少62%和35%。转移生物标志物显示，IVM治疗降低了波形蛋白和蜗牛蛋白的表达。该研究还发现，IVM减少了与转移相关的Wnt信号通路相关的Wnt5a/b和低密度脂蛋白受体相关蛋白6（LRP6）的表达。总之，IVM抑制内分泌耐药乳腺癌细胞转移中与EMT相关的Wnt信号通路。这些见解强调了将IVM重新用于内分泌耐药乳腺癌患者的潜力。
