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Evaluation of the effect of selective p110δ inhibitor on acute lymphoblastic leukemia cells
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P. Sadreazami   , A. Safar-Oughlou Azar , D. Bashash |
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| Keywords: Key words: Acute Lymphoid Leukemia, Apoptosis, Cell Cycle |
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Type of Study: Research |
Subject:
Hematology
Published: 2017/03/14
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Full-Text: (1885 Views) |
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Sci J Iran Blood Transfus Organ 2017; 14(1): 43-52
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Evaluation of the effect of selective p110δ inhibitor
on acute lymphoblastic leukemia cells
Sadreazami P.1, Safar-Oughlou Azar A.1, Bashash D.1
1Hematology Department, Faculty of Allied Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Abstract
Background and Objectives
The frequency of deregulated PI3K in acute lymphoblastic leukemia (ALL) coupled with the critical role of this signaling pathway in the acquisition of chemo-resistant phenotype lend compelling weight to the application of PI3K inhibitors for the treatment of ALL. In this study we aimed to evaluate the effect of selective p110δ inhibitor, GS-1101 on acute lymphoblastic leukemia Nalm-6 cells.
Materials and Methods
Nalm-6 cells were treated with different concentrations of GS-1101. In order to determine the cytotoxic and anti-proliferative effects of the drug, MTT and trypan blue exclusion assays were performed, respectively. Afterwards the effect of GS-1101 on cell cycle progression was evaluated using flowcytometry. Finally, Rq-PCR was applied to evaluate the mRNA expression level of cell cycle- and apoptotic-related genes in GS-1101-treated cells.
Results
Our results showed that GS-1101 not only reduced the number of viable cells but also hampered the metabolic activity of inhibitor-treated Nalm-6 cells both in dose- and time-dependent manner. Moreover, we found that the anti-proliferative effect of GS-1101 is mediated, at least partially, through the induction of G1 arrest as a result of up-regulated p21 expression level and accumulation of cells in sub-G1 phase of cell cycle. The results of Rq-PCR also demonstrated that GS-1101 exerts an inductive effect on the mRNA expression level of Bax, as the most important pro-apoptotic gene.
Conclusions
p110δ isoform inhibitor, GS-1101 shows both apoptotic and anti-proliferative effect on Nalm-6 cells through inducing cell-cycle arrest via up-regulation of cycline-dependent kinase inhibitor, p21 and upregulation of pro-apoptotic-related gene.
Key words: Acute Lymphoid Leukemia, Apoptosis, Cell Cycle
Received: 13 Nov 2016
Accepted: 1 Jan 2017
Correspondence: Bashash D., PhD of Hematology & Blood Banking. Assiatant Professor of Hematology Department, Faculty of Allied Medicine, Shahid Beheshti University of Medical Sciences.
Postal Code: 1971653312, Tehran, Iran. Tel: (+9821) 22721150; Fax: (+9821) 22721150
E-mail:
david_5980@yahoo.com
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Sadreazami P, Safar-Oughlou Azar A, Bashash D. Evaluation of the effect of selective p110δ inhibitor on acute lymphoblastic leukemia cells. Sci J Iran Blood Transfus Organ 2017; 14 (1) :43-52 URL: http://bloodjournal.ir/article-1-1090-en.html
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