سامانه مدیریت نشریات علمی دانشگاه علوم پزشکی مشهد

Tezcanli Kaymaz, Burcin, Selvi Gunel, Nur, Sogutlu, Fatma, Ozates Ay, Neslihan Pinar, Baran, Yusuf, Gunduz, Cumhur, Biray Avci, Cigir. (1401). Investigating the potential therapeutic role of targeting STAT3 for overcoming drug resistance by regulating energy metabolism in chronic myeloid leukemia cells. , 25(7), 904-912. doi: 10.22038/ijbms.2022.64138.14121
Burcin Tezcanli Kaymaz; Nur Selvi Gunel; Fatma Sogutlu; Neslihan Pinar Ozates Ay; Yusuf Baran; Cumhur Gunduz; Cigir Biray Avci. "Investigating the potential therapeutic role of targeting STAT3 for overcoming drug resistance by regulating energy metabolism in chronic myeloid leukemia cells". , 25, 7, 1401, 904-912. doi: 10.22038/ijbms.2022.64138.14121
Tezcanli Kaymaz, Burcin, Selvi Gunel, Nur, Sogutlu, Fatma, Ozates Ay, Neslihan Pinar, Baran, Yusuf, Gunduz, Cumhur, Biray Avci, Cigir. (1401). 'Investigating the potential therapeutic role of targeting STAT3 for overcoming drug resistance by regulating energy metabolism in chronic myeloid leukemia cells', , 25(7), pp. 904-912. doi: 10.22038/ijbms.2022.64138.14121
Tezcanli Kaymaz, Burcin, Selvi Gunel, Nur, Sogutlu, Fatma, Ozates Ay, Neslihan Pinar, Baran, Yusuf, Gunduz, Cumhur, Biray Avci, Cigir. Investigating the potential therapeutic role of targeting STAT3 for overcoming drug resistance by regulating energy metabolism in chronic myeloid leukemia cells. , 1401; 25(7): 904-912. doi: 10.22038/ijbms.2022.64138.14121

Investigating the potential therapeutic role of targeting STAT3 for overcoming drug resistance by regulating energy metabolism in chronic myeloid leukemia cells

Iranian Journal of Basic Medical Sciences
مقاله 15، دوره 25، شماره 7، مهر 2022، صفحه 904-912    اصل مقاله (502.44 K)
نوع مقاله: Original Article
شناسه دیجیتال (DOI): 10.22038/ijbms.2022.64138.14121
نویسندگان
Burcin Tezcanli Kaymaz* 1؛ Nur Selvi Gunel1؛ Fatma Sogutlu1؛ Neslihan Pinar Ozates Ay1؛ Yusuf Baran2؛ Cumhur Gunduz1؛ Cigir Biray Avci1
1Department of Medical Biology, Ege University Medicine Faculty, 35100, Izmir, Turkey
2Department of Molecular Biology and Genetics, Faculty of Science, Izmir Institute of Technology, 35433, Izmir, Turkey
چکیده
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.
کلیدواژه‌ها
Chemotherapeutic resistance؛ CML؛ Energy metabolism؛ Nilotinib؛ RNAi-based therapeutics؛ STAT3؛ Tyrosine kinase inhibitor
مراجع

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