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:: Volume 14, Issue 1 (Spring 2017) ::
Sci J Iran Blood Transfus Organ 2017, 14(1): 43-52 Back to browse issues page
Evaluation of the effect of selective p110δ inhibitor on acute lymphoblastic leukemia cells
P. Sadreazami , A. Safar-Oughlou Azar , D. Bashash
Abstract:   (4773 Views)

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.

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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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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Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Volume 14, Issue 1 (Spring 2017) Back to browse issues page
فصلنامه پژوهشی خون Scientific Journal of Iran Blood Transfus Organ
The Scientific Journal of Iranian Blood Transfusion Organization - Copyright 2006 by IBTO
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