Mohsen Soltanshahi - Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
Saeid Taghiloo - Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran
Hossein Asgarian-Omran - Immunogenetic Research Center, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
Hadi Hossein-Nataj - Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

Objectives: Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cells. The phosphatidylinositol 3-kinase/protein kinase B (Akt)/mechanistic target of rapamycin (PI3K/Akt/mTOR) pathway is amplified in 60-80% of patients with AML. Since this complex pathway is crucial to cell functions such as growth, proliferation, and survival, inhibition of this pathway would be postulated to inhibit leukemia initiation and propagation. Thus, blocking the PI3K/Akt/mTOR signal transduction network could be an effective new strategy for targeted anticancer therapy. Here, we highlight recent data generated with these new inhibitors against cancer cells and their potential as anticancer drugs. Methods: Firstly, we optimized drug concentration with MTT assay. Then we treated AML cell lines, HL-60 with Idelalisib as PI3K inhibitor, MK-2206 as Akt inhibitor and Everolimus as mTOR inhibitor for 48 hours, in the form of single, dual and triple treatment. Finally, the level of early and late apoptosis of HL-60 cell lines were evaluated using Flow cytometry Annexin-V/PI kit. Results: Our data indicated the early and late apoptosis were increased in single treatment of HL-60 with Idelalisib, MK-2206 and Everolimus compared with untreated cell lines. Also, dual and triple treatment were more significantly higher than single treatment and/or Untreated cells. Conclusion: The PI3K/Akt/mTOR signaling pathways are one of the important pathway to tumor progression. In conclusion, Idelalisib, MK-2206 and Everolimus exhibited in vitro antitumor activity on AML, HL-60 cell lines alone or in combination with together, suggesting potential application in AML therapy.

PI3K. Akt, mTOR, Idelalisib, MK-2206, Everolimus, AML