Figure 1.

PI3Kδ inhibition chemosensitizes through blockade of Ara-C mediated Akt-dependent survival signaling. (A) Western blot analysis of Akt and GSK3β phosphorylation in Nalm-6 and RCH-ACV cell lines over time following three hour exposure to Ara-C. Images are representative of 3 biologically independent replicates. (B) Schematic illustrating β-catenin reporter GFP transcription. (C) Representative image of flow cytometry gating strategy used to detect pAkt and β-catenin reporter GFP positivity following three hour exposure of cells to Ara-C. (D) β-catenin reporter GFP positivity detected over time by flow cytometry in Nalm-6 cells treated with vehicle or GS-649443 after three hour Ara-C exposure. Data are mean ± s.e.m.; unpaired two-sided Student’s t-test, n = 3 biologically independent experiments; p < 0.05, p < 0.01. (E) Proliferation over time of Nalm-6 cells treated with vehicle or GS-649443 after three hour exposure to post-Ara-C. Data are mean ± s.e.m.; unpaired two-sided Student’s t-test, n = 3 biologically independent experiments; p < 0.05. (F) Caspase-3 positivity in Nalm-6 cells as detected by flow cytome try following 72 h treatment with vehicle or GS-649443 after three hour exposure to Ara-C. Data are mean ± s.e.m.; unpaired two-sided Student’s t-test, n = 3 biologically independent experiments; p < 0.05.