Investigating the cytotoxic and apoptotic effects of sunitinib upon K-562 chronic myelogenous leukemia cell line and assessment of gene profiling.
J Cancer Res Ther
; 16(1): 150-156, 2020.
Article
em En
| MEDLINE
| ID: mdl-32362626
ABSTRACT
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 ANDMETHODS:
Sunitinib's effective dose cytotoxic IC50 was determined by trypan blue and WST-1 cell proliferation assay tests. Expression levels of target genes were determined by quantitative reverse transcriptase polymerase chain reaction simultaneously after sunitinib application. Protein expression analysis was determined by "WesternBreeze Chromogenic Kit-Anti-Rabbit" based on the principles of the application kit by Western blot analysis.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 48th 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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Leucemia Mielogênica Crônica BCR-ABL Positiva
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Biomarcadores Tumorais
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Regulação Neoplásica da Expressão Gênica
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Apoptose
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Proliferação de Células
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Sunitinibe
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Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Cancer Res Ther
Ano de publicação:
2020
Tipo de documento:
Article