Investigating the cytotoxic and apoptotic effects of sunitinib upon K-562 chronic myelogenous leukemia cell line and assessment of gene profiling.
Autor: | Ozkan MC; Department of Hematology, Ege University, School of Medicine, Izmir, Turkey., Kaymaz BT; Department of Medical Biology, Ege University, School of Medicine, Izmir, Turkey., Gunes A; Department of Hematology, Ege University, School of Medicine, Izmir, Turkey., Can BK; Department of Medical Biology, Ege University, School of Medicine, Izmir, Turkey., Soyer NA; Department of Hematology, Ege University, School of Medicine, Izmir, Turkey., Yilmaz AF; Department of Hematology, Ege University, School of Medicine, Izmir, Turkey., Vural F; Department of Hematology, Ege University, School of Medicine, Izmir, Turkey., Sahin F; Department of Hematology, Ege University, School of Medicine, Izmir, Turkey., Saydam G; Department of Hematology, Ege University, School of Medicine, Izmir, Turkey. |
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Jazyk: | angličtina |
Zdroj: | Journal of cancer research and therapeutics [J Cancer Res Ther] 2020 Jan-Mar; Vol. 16 (1), pp. 150-156. |
DOI: | 10.4103/jcrt.JCRT_983_17 |
Abstrakt: | Objective: Tyrosine kinase inhibitors (TKIs) which efficiently inhibit BCR-ABL are highly effective for clinical treatment of chronic myeloid leukemia (CML), but development of resistance to TKIs is a big challenge to treatment. Sunitinib is a multitargeted TKI targeting vascular endothelial growth factor receptor and is defined a safe and effective candidate target, but its effect on other signaling pathways is unknown. To investigate the cytotoxic and apoptotic effect of sunitinib in CML cell model K-562 on JAK-STAT signaling pathway components, suppressor genes and oncogenes, hematopoiesis-related genes, cell cycle and VEGF pathway components, and mRNA level expression changes was aimed. Materials and Methods: Sunitinib's effective dose cytotoxic IC Results: Assessing the cytotoxicity of K-562 cells following sunitinib treatment revealed that sunitinib decreased cell proliferation in a time- and dose-dependent manner. According to the sunitinib inhibition curve, IC50 dose was calculated as 3.5 μM at 48 th h for K-562 cells and apoptosis assays pointed that sunitinib induces apoptotic cell death of leukemic cells at moderate levels. Conclusion: Our study supports that sunitinib might be used as a novel therapeutic target to trigger apoptosis in CML cells which in turn might accelerate therapeutic response in regard to inhibiting oncogenes and enhancing tumor suppressors in cooperation with cell cycle regulatory genes. Competing Interests: None |
Databáze: | MEDLINE |
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