三阴性乳腺癌 (TNBC) 中的癌症干细胞 (CSC) 被认为是极具挑战性的细胞亚群，以其高复发倾向和不良预后而闻名。莫能菌素是一种离子导入抗生素，据报道对多种癌症，尤其是癌症干细胞具有显着的治疗功效。厄洛替尼被归类为 EGFR-TKI 之一，之前已被确定为 TNBC 的有前景的治疗靶点。我们的研究旨在评估莫能菌素和厄洛替尼组合作为 TNBC 潜在治疗策略的有效性。通过各种体外测定，包括细胞毒性测定、集落形成测定、伤口愈合，评估莫能菌素和厄洛替尼组合的潜在抗癌活性测定、Transwell 测定、微球形成测定和 CSC 比例测定。此外，利用荷瘤裸鼠进行体内研究，评估莫能菌素与厄洛替尼联合用药对肿瘤生长的抑制作用。结果表明，莫能菌素与厄洛替尼联合用药可协同抑制细胞增殖、迁移率、侵袭能力。并降低体内和体外CSCs比例以及CSC标志物SOX2和CD133。此外，莫能菌素和厄洛替尼在体内和体外联合治疗同时抑制EGFR/ERK和PI3K/AKT信号通路中涉及的主要蛋白。同时抑制EGFR/ERK和PI3K/AKT/mTOR莫能菌素和厄洛替尼组合的信号通路在抑制 TNBC 中的肿瘤增殖和癌细胞干性方面表现出协同作用。© 2024。作者获得 Springer Science Business Media, LLC（Springer Nature 旗下公司）的独家许可。

Cancer stem cells (CSCs) in triple-negative breast cancer (TNBC) are recognized as a highly challenging subset of cells, renowned for their heightened propensity for relapse and unfavorable prognosis. Monensin, an ionophoric antibiotic, has been reported to exhibit significant therapeutic efficacy against various cancers, especially CSCs. Erlotinib is classified as one of the EGFR-TKIs and has been previously identified as a promising therapeutic target for TNBC. Our research aims to assess the effectiveness of combination of monensin and erlotinib as a potential treatment strategy for TNBC.The combination of monensin and erlotinib was assessed for its potential anticancer activity through various in vitro assays, including cytotoxicity assay, colony formation assay, wound healing assay, transwell assay, mammosphere formation assay, and proportion of CSCs assay. Additionally, an in vivo study using tumor-bearing nude mice was conducted to evaluate the inhibitory effect of the monensin and erlotinib combination on tumor growth.The results indicated that combination of monensin with erlotinib synergistically inhibited cell proliferation, the migration rate, the invasion ability and decreased the CSCs proportion, and CSC markers SOX2 and CD133 in vivo and in vitro. Furthermore, the primary proteins involved in the signaling pathways of the EGFR/ERK and PI3K/AKT are simultaneously inhibited by the combination treatment of monensin and erlotinib in vivo and in vitro.The simultaneous inhibition of the EGFR/ERK and PI3K/AKT/mTOR signaling pathways by the combination of monensin and erlotinib exhibited a synergistic effect on suppressing tumor proliferation and cancer cell stemness in TNBC.© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.