Synergistic growth-inhibitory and apoptosis-inducing effects between the IGFR inhibitor NVP-AEW541 and PI3K/Akt/mTOR inhibitors (MK2206, BEZ235, and RAD001). (A) Median dose-effect analysis of synergistic growth-inhibitory effects. Growth inhibition was measured by MTT assay. CI was calculated using the CI-isobologram method; CI = 1, additive effect; CI < 1, synergistic effect; CI > 1, antagonistic effect. The concentrations of the drug used for MTT assay and the original CI (combination index) values of each drug combination were summarized in Additional file 1: Table S1. (B and C) Synergistic apoptosis-inducing effects between NVP-AEW541 and MK2206, BEZ235, and RAD001 in HCC cells and HUVECs measured by flow cytometry (sub-G1 fraction analysis, B) and by PARP cleavage and caspase3 activation (Western blotting, C). Columns, mean averages of three independent experiments; bars, SD. **, p < 0.01 compared with cells treated with a single inhibitor.