Fig 2: Regulation of downstream signaling following PI3K pathway inhibition in T-ALL cell linesSeven T-ALL cell lines were treated with AZD2014 (0.25 μM), AZD5363 (1 μM), AZD8186 (0.5 μM) and AZD8835 (0.5 μM) for the times indicated. Western blot analysis was performed to determine modulation of the indicated proteins and phosphorylated proteins following pathway inhibition (n = 2).

Fig 3: A cancer cell line pharmacology screen of PI3K pathway inhibitors identified strong activity of AKT and mTORC1/2 inhibitors in hematological malignancies971 cancer cell lines were screened against four PI3K pathway inhibitors and IC50 values determined. (A) Tree map depicting the distribution of 971 cancer cell lines across 24 lineages. Figures in parentheses represent the numbers of cell lines. (B–E) Elastic net regularization analysis for AZD5363 (B), AZD2014 (C), AZD8186 (D) and AZD8835 (E). The coefficient value signifies the correlation between sensitivity (IC50 value) and the input variable (e.g. genetic aberration/lineage) based on elastic net regression analysis, with a larger positive or negative coefficient representing a more significant correlation. Blue bars represent lineage input variables and orange bars represent genetic aberration input variables. (F) Tree map depicting the distribution of 164 hematological cancer cell lines across different hematological subtypes. Pale blue box represents “Myeloma_other” (1). Figures in parentheses represent the numbers of cell lines. (G) Waterfall plot of T-cell acute lymphoblastic leukemia (T-ALL), B-cell acute lymphoblastic leukemia (B-ALL), chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL) and non-Hodgkin lymphoma (NHL) cancer cell lines ordered according to sensitivity to AZD5363.

Fig 4: a–c Clonogenic assay of the cell lines SUM159, MDA-MB-231, and BT549 after transient silencing of the putative miR-1287-5p target PIK3CB leads to a similar phenotype compared to miR-1287 overexpression in the cell lines. Cells develop less colonies after PIK3CB silencing (a, b) and PIK3CB silencing also leads to a G1 Phase Arrest (c) in all four cell lines. d–g SUM159 and BT549 cells treated with two different concentrations of PI3Kinase inhibitors in combination with control scrambled RNA (10 µM of Allstar negative control) or the miR-1287-5p mimics (10 µM of miR-1287-5p mimics) (d, e) CAL101 (Idelalisib) and f, g BYL719 (Alpelisib). Cells treated with miR-1287-5p mimic are more sensitive to CAL-101 and BYL719 treatment in both tested cell lines compared to cells treated with the scrambled control RNA. *p < 0.05

Fig 5: Inhibitory effect on PI3K/Akt/NF-κB signaling pathway in HepG2 cells. Effect of PI3K inhibitor and SCU-induced inhibition of p-PI3K, p-Akt, and p-IκB-α levels in HepG2 cells. Cells were treated with or without 20 μM of PI3K inhibitor: LY294002 and 100 μM of SCU for 48 h. The results obtained from three independent experiments were expressed as mean ± standard deviation (SD) compared with the control group. * p < 0.05, ** p < 0.01, *** p < 0.001.