Fig. 4

Nelarabine combined with the PI3K inhibitor ZSTK-474 induces cytotoxicity and causes a down-modulation of PI3K, MEK, and Bcl2 signaling. a Cell viability assays of T-ALL cell lines treated for 48 h with increasing concentrations of nelarabine combined with the pan PI3K p110 inhibitor ZSTK-474, the γ/δ PI3K p110 inhibitor IPI-145, the MEK inhibitor trametinib, or the Bcl2 inhibitor ABT199 at fixed ratios. Results are the mean of three different experiments ± SD. b Western blotting analyses documenting a marked decrease in the phosphorylation of AKT, S6RP, and ERK in T-ALL cell lines treated with the combination of nelarabine (10 μM) and ZSTK-474 (2.5 μM). Molecular weights are indicated on the right. One representative of three different experiments is shown. c Western blotting analyses of T-ALL cell lines treated with the combination of nelarabine (10 μM) and ZSTK-474 (2.5 μM) for 48 h. The combined treatment decreased the levels of expression of Bcl2 and Bcl-xL and increased the expression of the pro-apoptotic Bax and Bak proteins. Antibody to β-actin served as a loading control. Molecular weights are indicated on the right. One representative of three different experiments is shown