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Induction of p21- and p27-mediated cell cycle arrest in Nalm-6 cells using pan-PI3K inhibitor (Buparlisib)
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A. va Safaroghli-Azar   , Mohammadreza Sadri , Davood Bashash |
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Abstract: (3817 Views) |
| Introduction: In the era of targeted therapies, efforts are being made to identify the novel agents with strong anti-tumor activity in order to improve cure rates of human malignancies while reducing the toxic side effects of intensive regimens. Increasing number of genetic and cancer biology studies indicated a prominent role for the aberrant activation of PI3K/Akt pathway in not only the pathogenesis of acute lymphoblastic leukemia (ALL), but also in acquisition of chemo-resistant phenotype. In this study we aimed to assess the anti-proliferative effect of pan class I PI3K inhibitor, Buparlisib, on Nalm-6 cells.
Materials and Methods: To evaluate whether inhibition of PI3K using Buparlisib could exert anti-proliferative effect in leukemic cells, Nalm-6 were subjected to different concentrations of the inhibitor and subsequent cell viability, cell count, cell cycle progression and transcriptional alteration of cell cycle-related genes were investigated.
Results: Buparlisib not only decreased the number of viable inhibitor-treated cells in a concentration and time-dependent manner, but also reduced the survival rate of Nalm-6 cells. Furthermore, we found that the anti-proliferative effect of this inhibitor is mediated, at least partially, through induction of G1 arrest as a result of up-regulated p21 and p27 and down-regulated c.Myc expression level.
Conclusion: The present study showed that Buparlisib decreased the proliferative capacity of Nalm-6 cells probably via reduction in DNA synthesize rate, induction of cell cycle arrest and alteration in the expression level of proliferative-related genes. The results suggest that PI3K inhibitors may be used as a promising therapeutic strategy for the treatment of ALL patients. |
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| Keywords: Cell cycle, Acute Lymphoblastic Leukemia, PI3K Pathway, Buparlisib, Nalm-6 |
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Full-Text [PDF 1879 kb]
(753 Downloads)
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Type of Study: Research |
Subject:
General
Received: 2017/11/8 | Accepted: 2018/03/11 | Published: 2018/09/23
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