Affiliations: [a] Department of Laboratory Sciences, School of Paramedical Sciences, Mashhad University of Medical Sciences, Mashhad, Iran | [b] Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran | [c] School of Pharmacy, University of Waterloo, Waterloo, ON, Canada | [d] Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
Correspondence:
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Corresponding author: Fatemeh Mosaffa, Professor of Pharmaceutical Biotechnology, Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, 91775-1365, Iran; and Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, 91775-1365, Iran. Tel.: 051 31801204; Fax: 051 38823251; E-mail: MosaffaF@mums.ac.ir
Abstract: BACKGROUND:Chronic inflammation is considered to be a risk factor for carcinogenesis, tumor development and metastasis by providing tumor-related factors. OBJECTIVES:We aimed to evaluate the effect of cytokine interleukin-1β (IL-1β) as a key mediator of inflammation on multidrug resistance associated protein 2 (MRP2) expression and tamoxifen toxicity in estrogen receptor positive (ER+) MCF-7 breast cancer cells. METHODS:The effects of IL-1β on tamoxifen toxicity following 20-day treatment of MCF-7 cells with IL-1β and/or 17β-estradiol (E2) were measured by MTT assay. Furthermore, the effects of IL-1β and/or E2 on the mRNA expression and protein levels of MRP2 and NF-κB (p65) in breast cancer cells were evaluated by QRT-PCR and Western blot analysis, respectively. RESULTS:Treatment of breast cancer cells with IL-1β+ E2 decreased the sensitivity to 4-OH tamoxifen compared to both E2-treated and untreated cells. The mRNA expression levels of MRP2 and NF-κB (p65) were significantly increased following treatment with IL-1β+ E2, compared to control. In addition, breast cancer cells treatment with IL-1β+ E2 increased protein expression of MRP2 and it had no significant effect on NF-κB/p65 protein expression in these cells. CONCLUSION:Increased expression of mRNA and protein level of MRP2 following 20-day treatment of MCF-7 cells with IL-1β + E2 might be a possible elucidation for the increased tamoxifen resistance which was observed in these cells. More researches are essential to clarify the molecular mechanisms of inflammation on drug-resistance in the tumor environment in order to reducing or eliminating chemotherapy resistance and developing more effective treatment strategies.
Keywords: IL-1β, MRP2, NF-κB/p65, Tamoxifen, breast cancer
DOI: 10.3233/BD-201056
Journal: Breast Disease, vol. 40, no. 4, pp. 263-268, 2021
