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Anti–Muc1 Nanobody Can Synergize the Tamoxifen and Herceptin Effects on Breast Cancer Cells by Inducing Er, Pr and Her2 Overexpression Publisher Pubmed



Shokrollahi Barough M1, 2, 3 ; Jalili N2 ; Shafiee S2 ; Salehi M2 ; Naseri N2 ; Javidi MA4 ; Hosseinzadeh A2 ; Farahmand L2
Authors
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Authors Affiliations
  1. 1. ATMP Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, 1517964311, Iran
  2. 2. Recombinant Proteins Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran
  3. 3. Department of Immunology, Iran University of Medical Sciences, Tehran, 1449614535, Iran
  4. 4. Integrative Oncology Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran

Source: International Immunopharmacology Published:2023


Abstract

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. © 2023 Elsevier B.V.