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Potentiation of growth suppression and modulation of multidrug resistance by gamma and beta interferons in the MDA-MB-231 breast cancer cell line
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Pouya Ghaderi   , Hamid Reza Jalili , Mobin Mohammadi , Mohammad Reza Rahmani |
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Abstract: (308 Views) |
Introduction: Multi-drug resistance (MDR) might be acquired by the cancer cells during chemotherapy, and ATP-binding cassette (ABC) transporters play a significant role in MDR. Interferon-γ (IFN-γ) and IFN-β can inhibit cancer cell proliferation; however, the effects and mechanism of these cytokines on growth and MDR are still unclear.
Methods and Materials: Using the MDA-MB-231 cell line, we assessed the effects of 20, 100, and 500 IU/ml of IFN-γ and IFN-β, alone or in combination, on cell viability by the methyl thiazolyl tetrazolium (MTT) assay, and then we performed the Uptake and Efflux experiment to evaluate the effect of these IFNs on the cell resistance. Then, using quantitative real-time PCR, we evaluated changes in the expression of ABCB1, ABCC1, and ABCG2 mRNA levels.
Results: We discovered that IFN-γ and IFN-β may both reduce viability, either alone or in combination. The combination of IFNs also displayed synergistic responses, particularly when utilizing equivalent dosages of 500 or 100 IU/ml. The combination of IFN-γ and IFN-β resulted in a significant increase in doxorubicin accumulation and down-regulation of the ABCC1 gene at the mRNA level.
Conclusion: Our study suggested that equal doses of IFN-γ and IFN-β in combination may result in potentiated responses against cancer, especially when combined with chemotherapy agents.
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| Keywords: Combinational therapy, Chemotherapy, Interferon beta, Interferon gamma, Multi-drug resistance, ATP-binding cassette transporter |
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Full-Text [PDF 323 kb]
(40 Downloads)
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Type of Study: Research |
Subject:
General
Received: 2023/12/10 | Accepted: 2023/08/23 | Published: 2023/08/23
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