Combination Effect of Notch1 and Pi3k / Akt / Mtor Signaling Pathways Inhibitors on T-All Cell Lines

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.