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Anti-cancer effect of phosphatidylinositol 3-kinase inhibitor on NB4 leukemic cells
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Mahda Delshad1   , Ava Safaroghli-Azar1 , Davood Bashash 2 |
1- Department of Hematology and Blood banking, School of Allied Medicine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
2- Department of Hematology and Blood Banking, School of Allied Medical Sciences, Tehran, Iran. , d.bashash@sbmu.ac.ir |
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Abstract: (4359 Views) |
Background and Aim: In the last decades, experimental studies have shown that aberrant activation of phosphatidylinositol 3-kinase (PI3K) pathway is an essential step for both initiation and maintenance of tumorgenesis in a wide range of human cancers, such as, acute promyelocytic leukemia (APL). In this study, we investigated the cytotoxic effect of BKM120, a pan-PI3K inhibitor, on APL-derived NB4 cells.
Material and Methods: To evaluate the inhibitory effect of BKM120 on PI3K/AKt pathway, we analyzed the expression and phosphorylation level of Akt using western blot. Using western blot, phosphorylation rate of Akt was evaluated. In order to evaluate the effect of the inhibitor on the metabolic activity, apoptosis index and alteration of the expression of apoptotic-related genes, we used MTT assay, annexin-V/PI staining and RT-PCR analysis respectively. Using SPSS 17 software data were analyzed by t-test.
Results: We found that inhibition of PI3K/Akt pathway by BKM120 resulted in reduction of metabolic activity of APL-derived NB4 cells in a dose- and time-dependent manner (p≤ 0.001). Moreover, the results obtained from flowcytometry and RT-PCR analysis showed a significant increase in BKM120 induced apoptotic cell death in the inhibitor-treated cells (p≤ 0.001). We found BKM120 increased iBax/Bcl-2 transcriptional ratio (p≤ 0.001).
Conclusion: BKM-120 exerts a favorable apoptotic effect on NB4 cells through inhibition of the PI3K/Akt signaling pathway.
Key words: Apoptosis, Phosphatidylinositol 3-kinase, Acute promyelocytic leukemia, NB4, BKM120.
Received: Jan 24, 2017 Accepted: Aug 12, 2017 |
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| Keywords: Apoptosis, Phosphatidylinositol 3-kinase, Acute promyelocytic leukemia, NB4, BKM120. |
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Full-Text [PDF 3924 kb]
(1124 Downloads)
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Type of Study: Original Research |
Subject:
General
Received: 2017/11/15 | Accepted: 2017/11/15 | Published: 2017/11/15
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