Fig. 4.

Combination of pan-PI3K and MLK3 inhibitors, or dual PI3K/mTOR and MLK3 inhibitors failed to exert synergism on glioblastoma cell proliferation. a, b U-251 MG and U-343 MG cells were treated with the pan-PI3K inhibitor BKM120 or the dual PI3K/mTOR inhibitor PQR309 alone at different concentrations. Cell viability was evaluated by MTT method in 48 h. c, d Fa-CI plots of BKM120 and URMC-099, and PQR309 and URMC-099 in fixed ratios (BKM120:URMC-099 = 2:3; PQR309:URMC-099 = 4:3). Two dashed lines indicated the CI values of 0.9 and 1.1. e, f Combination effect of BKM120 and URMC-099, or PQR309 and URMC-099 on the proliferation of U-251 MG and U-343 MG cells. Cells were treated with inhibitors for 48 h. P values were determined by Two-way ANOVA and Post Hoc multiple comparison Tukey HSD test. *: p < 0.05; **: p < 0.01; ***: p < 0.001