Fig. 4

Characterization of the anti-glioma activity of a combination treatment of BKM120 and TH588. a Single and combinatorial titration of BKM120 and TH588 in a 3-day growth assay in U251 cell lines. b Analysis of the BKM120 and TH588 interaction and the resulting Fa-CI plots (fraction affected Combination Index). For U251, most Combination Index values fell below the CI = 1 line, which indicates synergy of the combination of BKM120 and TH588. c Synergy plots generated by Combenefit showing the interaction between BKM120 and TH588. Analysis of interaction resulted in HSA (high single agent) values and Bliss values (n = 3, technical replicates), indicating synergistic efficacy as calculated from expected and observed growth inhibition. HSA and Bliss values > 0 indicate synergistic effects. d–f Same as (a–c) but for LN229 cells. g Images of colonies formed by several GBM cell lines incubated with TH588, BKM120, or a combination of both for 14 days followed by Giemsa Stain solution on the last day of incubation. h–k Three-dimensional (3D) imaging of DMSO or matrix doses of drugs in neurobasal medium on day 15 at 10× magnification and 250 ms exposure. The scale bar is 250 µm