期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 124, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.intimp.2023.110792
关键词
Drug resistance; Immunofluorescence staining; Apoptosis; 3D spheroid; Synergistic effect
Blocking MUC1 resulted in overexpression of ER, PR, and HER2, leading to increased drug hypersensitization and reduced IC50 levels for Tamoxifen and Herceptin. MCF-7R cells showed positive response to Tamoxifen with decreased IC50 and enhanced apoptosis.
Introduction: 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.Material and Methods: 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.Results: 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.Conclusion: The ER, PR, and HER2 overexpression after MUC1 blocking could signal drug hypersensitization and facilitate drug resistance management.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据