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Title

Positive Effects of PI3K/Akt Signaling Inhibition on PTEN and P53 in Prevention of Acute Lymphoblastic Leukemia Tumor Cells

Pages

  470-480

Abstract

 Purpose: The ALL&fgrp=ALL&fyrs=ALL" target="_blank">PI3K/Akt signaling pathway regulates cell growth, proliferation and viability in hematopoietic cells. This pathway always dysregulates in acute lymphoblastic leukemia (ALL). PTEN and P53 are tumor suppressor genes correlated with ALL&fgrp=ALL&fyrs=ALL" target="_blank">PI3K/Akt signaling pathway, and both have a tight link in regulation of cell proliferation and cell death. In this study, we investigated the effects of dual targeting of PI3K/Akt pathway by combined inhibition with nvp-ALL&fgrp=ALL&fyrs=ALL" target="_blank">BKM-120 (PI3K inhibitor) and ALL&fgrp=ALL&fyrs=ALL" target="_blank">MK-2206 (Akt inhibitor) in relation with PTEN and P53 on apoptosis and proliferation of leukemia cells. Methods: Both T and B ALL cell lines were treated with both inhibitors alone or in combination with each other, and induction of apoptosis and inhibition of proliferation were evaluated by flow cytometry. Expression levels of PTEN as well as P53 mRNA and protein were measured by real-time qRT-PCR and western blot, respectively. Results: We indicated that both inhibitors (ALL&fgrp=ALL&fyrs=ALL" target="_blank">BKM-120 and ALL&fgrp=ALL&fyrs=ALL" target="_blank">MK-2206) decreased cell viability and increased cytotoxicity in leukemia cells. Reduction in Akt phosphorylation increased PTEN and P53 mRNA and P53 protein level (in PTEN positive versus PTEN negative cell lines). AdditionALLy, both inhibitors, particularly in combination with each other, increased apoptosis (evaluated with Annexin V and caspase 3) and reduced proliferation (Ki67 expression) in leukemia cells. However, administration of IL7 downregulated PTEN and P53 mRNA expression and rescued cancer cells following inhibition of ALL&fgrp=ALL&fyrs=ALL" target="_blank">BKM-120 and ALL&fgrp=ALL&fyrs=ALL" target="_blank">MK-2206. Conclusion: This investigation suggested that inhibition of Akt and PI3K could be helpful in leukemia treatment.

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    APA: Copy

    Naderali, Elahe, Valipour, Behnaz, KHAKI, AMIR AFSHIN, Soleymani Rad, Jafar, ALIHEMMATI, ALIREZA, RAHMATI, MOHAMMAD, & NOZAD CHAROUDEH, HOJJATOLLAH. (2019). Positive Effects of PI3K/Akt Signaling Inhibition on PTEN and P53 in Prevention of Acute Lymphoblastic Leukemia Tumor Cells. ADVANCED PHARMACEUTICAL BULLETIN, 9(3), 470-480. SID. https://sid.ir/paper/740316/en

    Vancouver: Copy

    Naderali Elahe, Valipour Behnaz, KHAKI AMIR AFSHIN, Soleymani Rad Jafar, ALIHEMMATI ALIREZA, RAHMATI MOHAMMAD, NOZAD CHAROUDEH HOJJATOLLAH. Positive Effects of PI3K/Akt Signaling Inhibition on PTEN and P53 in Prevention of Acute Lymphoblastic Leukemia Tumor Cells. ADVANCED PHARMACEUTICAL BULLETIN[Internet]. 2019;9(3):470-480. Available from: https://sid.ir/paper/740316/en

    IEEE: Copy

    Elahe Naderali, Behnaz Valipour, AMIR AFSHIN KHAKI, Jafar Soleymani Rad, ALIREZA ALIHEMMATI, MOHAMMAD RAHMATI, and HOJJATOLLAH NOZAD CHAROUDEH, “Positive Effects of PI3K/Akt Signaling Inhibition on PTEN and P53 in Prevention of Acute Lymphoblastic Leukemia Tumor Cells,” ADVANCED PHARMACEUTICAL BULLETIN, vol. 9, no. 3, pp. 470–480, 2019, [Online]. Available: https://sid.ir/paper/740316/en

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