针对乳腺癌靶向治疗的一个最紧迫的问题是对于他莫昔芬和赫赛汀的耐药性。这种药物耐药性通常表现为某些细胞表面受体的表达减少。一些生物调控可以诱导这些受体的明显过表达，以有利于药物的敏感性。在这项研究中，2D和3D培养的药物敏感性MCF-7和SKBR-3以及药物耐药性MCF-7R（对他莫昔芬耐药）和JIMT-1（对赫赛汀耐药）乳腺癌细胞系被暴露于抗MUC1纳米抗体，并使用qRT-PCR和免疫荧光染色分析评估其ER、PR和HER2基因和蛋白表达。MTT实验和CompuSyn软件随后确定细胞存活率和联合治疗的协同关系。通过Annexin V/PI和AO/EB染色评估细胞凋亡。抗MUC1暴露提高了ER（42倍）、PR（18.5倍）和HER2（4.7倍）的表达水平。由于联合治疗，他莫昔芬和赫赛汀的IC50水平分别降低了10倍和3倍。MCF-7R细胞对于他莫昔芬呈现积极反应，IC50下降了5倍，并增强了凋亡。MUC1阻断后的ER、PR和HER2过表达可能预示着药物超敏感性，并有助于药物耐药性管理。版权 © 2023 Elsevier B.V. 保留所有权利。

One of the most pressing concerns associated with breast cancer-targeted therapies is resistance to Tamoxifen and Herceptin. Such drug resistance is usually characterized by reduced expression of certain cell surface receptors. Some biological regimens can induce perceptible overexpression of these receptors in favor of drug responsiveness.In this research, drug-responsive MCF-7 and SKBR-3, along with drug-resistant MCF-7R (Tamoxifen resistant) and JIMT-1 (Herceptin resistant) breast cancer cell lines in 2D and 3D cultures were exposed to anti-MUC1 nanobody and then assessed for their ER, PR, and HER2 gene and protein expression using qRT-PCR and immunofluorescent staining analyses. Cell viability and the synergistic relationships of combination treatments were determined with MTT assay followed by CompuSyn software. Apoptotic cells were evaluated with Annexin V/propidium Iodide (PI) and acridine orange/ethidium bromide (AO/EB) staining.Anti-MUC1 exposure elevated the expression levels of ER (42 folds), PR (18.5 folds), and HER2 (4.7 folds). As a result of co-treatment, the IC50 levels for Tamoxifen and Herceptin were reduced by up to 10 and 3 folds, respectively. MCF-7R cells responded positively to Tamoxifen, as evidenced by a 5-fold reduction in the IC50 and enhanced apoptosis.The ER, PR, and HER2 overexpression after MUC1 blocking could signal drug hypersensitization and facilitate drug resistance management.Copyright © 2023 Elsevier B.V. All rights reserved.