Tehran University of Medical Sciences International Journal of Hematology-Oncology and Stem Cell Research 2008-2207 14 2 2020 04 07 99 109 Halimeh Khoshamooz Department of Hematology and Blood Banking, Faculty of Medicine, Tarbiat Modares University, Tehran, Iran Saeid Kaviani Department of Hematology, Faculty of Medicine, Tarbiat Modares University, Tehran, Iran Amir Atashi Department of Basic Sciences, School of Medicine, Shahroud University of Medical Sciences, Shahrood, Iran Seyed Hossein Mirpour Hassankiadeh Department of Internal Medicine, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran 2019 08 05 2019 10 07 Background: Acute T lymphoblastic Leukemia (T-ALL) is a highly aggressive hematologic malignancy. Chemotherapy resistance is one of the most important challenges in T-ALL treatment. Alterations in cellular signaling pathways such as Notch1 and PI3K / AKT / mTOR play a role in cell proliferation, survival, and resistance to chemotherapy. Combination of Notch1 and PI3K / AKT / mTOR inhibitors is an interesting and rational strategy in treatment of T-ALL. Interaction of AZD5363 as an inhibitor of PI3k / AKT / mTOR and Compound E as an inhibitor of Notch1 signaling pathway was investigated in a T-ALL pre-clinical model. Materials and Methods: T-ALL cell lines included Jurkat, Molt-4, and HPB- ALL cells were treated with AZD5363 and Compound E alone and in combination. Cell viability was determined by MTT assay. Flow cytometry was used to measure apoptosis. Interaction between AZD5363 and Compound E was assessed by Chou-Talalay method. Results: Combination treatment with AZD5363 and Compound E decreased cell viability with synergistic effect in all cell lines at 72 hours. Drug combination increased apoptosis even in Jurkat and HPB-ALL cells resistant to Compound E and AZD5363, respectively. Conclusion: Combination of AZD5363 with Compound E in T-ALL cell lines exhibited a synergistic effect. Cytotoxicity of drug combination increased in all T-ALL cell lines compared to each as a single drug. Simultaneous inhibition of Notch1 and PI3K / AKT signaling pathways as a possible treatment of T-ALL, provides a basis for future investigations. https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/view/1166 https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/download/1166/818