The effect of IL-1β on MRP2 expression and tamoxifen toxicity in MCF-7 breast cancer cells

• Published in: Breast disease Vol. 40; no. 4; pp. 263 - 268
• Main Authors: Valinezhad Sani, Fatemeh, Alamolhodaei, Nafiseh Sadat, Rashidpoor, Hatam, Gharaee, Melika Ehtesham, Behravan, Javad, Mosaffa, Fatemeh
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 30.09.2021
• Subjects: Antineoplastic Agents, Hormonal - pharmacology; Breast Neoplasms - pathology; Estradiol - pharmacology; Estrogens - pharmacology; Female; Humans; Interleukin-1beta - pharmacology; MCF-7 Cells; Multidrug Resistance-Associated Protein 2 - genetics; Multidrug Resistance-Associated Protein 2 - metabolism; NF-kappa B - genetics; NF-kappa B - metabolism; RNA, Messenger - metabolism; Tamoxifen - pharmacology; NF-κB/p65; breast cancer; MRP2; IL-1β; Tamoxifen
• ISSN: 0888-6008; 1558-1551
• DOI: 10.3233/BD-201056

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.