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Iranian Journal of Basic Medical Sciences، جلد ۲۵، شماره ۷، صفحات ۹۰۴-۹۱۲
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| عنوان فارسی |
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| چکیده فارسی مقاله |
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| کلیدواژه‌های فارسی مقاله |
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| عنوان انگلیسی |
Investigating the potential therapeutic role of targeting STAT3 for overcoming drug resistance by regulating energy metabolism in chronic myeloid leukemia cells |
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| چکیده انگلیسی مقاله |
Objective(s): STATs are one of the initial targets of emerging anti-cancer agents due to their regulatory roles in survival, apoptosis, drug response, and cellular metabolism in CML. Aberrant STAT3 activity promotes malignancy, and acts as a metabolic switcher in cancer cell metabolism, contributing to resistance to TKI nilotinib. To investigate the possible therapeutic effects of targeting STAT3 to overcome nilotinib resistance by evaluating various cellular responses in both sensitive and nilotinib resistant CML cells and to test the hypothesis that energy metabolism modulation could be a mechanism for re-sensitization to nilotinib in resistant cells.Materials and Methods: By using RNAi-mediated STAT3 gene silencing, cell viability and proliferation assays, apoptotic analysis, expressional regulations of STAT mRNA transcripts, STAT3 total, pTyr705, pSer727 protein expression levels, and metabolic activity as energy metabolism was determined in CML model K562 cells, in vitro.Results: Targeting STAT3 sensitized both parental and especially nilotinib resistant cells by decreasing leukemic cell survival; inducing leukemic cell apoptosis, and decreasing STAT3 mRNA and protein expression levels. Besides, cell energy phenotype was modulated by switching energy metabolism from aerobic glycolysis to mitochondrial respiration in resistant cells. RNAi-mediated STAT3 silencing accelerated the sensitization of leukemia cells to nilotinib treatment, and STAT3-dependent energy metabolism regulation could be another underlying mechanism for regaining nilotinib response.Conclusion: Targeting STAT3 is an efficient strategy for improving the development of novel CML therapeutics for regaining nilotinib response, and re-sensitization of resistant cells could be mediated by induced apoptosis and regulation in energy metabolism. |
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| کلیدواژه‌های انگلیسی مقاله |
Chemotherapeutic resistance, CML, Energy metabolism, Nilotinib, RNAi-based therapeutics, STAT3, Tyrosine kinase inhibitor |
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| نویسندگان مقاله |
| Burcin Tezcanli Kaymaz
Department of Medical Biology, Ege University Medicine Faculty, 35100, Izmir, Turkey
| Nur Selvi Gunel
Department of Medical Biology, Ege University Medicine Faculty, 35100, Izmir, Turkey
| Fatma Sogutlu
Department of Medical Biology, Ege University Medicine Faculty, 35100, Izmir, Turkey
| Neslihan Pinar Ozates Ay
Department of Medical Biology, Ege University Medicine Faculty, 35100, Izmir, Turkey
| Yusuf Baran
Department of Molecular Biology and Genetics, Faculty of Science, Izmir Institute of Technology, 35433, Izmir, Turkey
| Cumhur Gunduz
Department of Medical Biology, Ege University Medicine Faculty, 35100, Izmir, Turkey
| Cigir Biray Avci
Department of Medical Biology, Ege University Medicine Faculty, 35100, Izmir, Turkey
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| نشانی اینترنتی |
https://ijbms.mums.ac.ir/article_20647.html |
| فایل مقاله |
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| کد مقاله (doi) |
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| زبان مقاله منتشر شده |
en |
| موضوعات مقاله منتشر شده |
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| نوع مقاله منتشر شده |
Original Article |
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