Table 1.

Synergistic inhibition of cell proliferation by MK-2206 combined with erlotinib or lapatinib in 14 tumor cell lines

Cell lineCancer typeCombination indexIC50 (μmol/L)Genotypes
ED50ED75ED90MK-2206Erlotinib/LapatinibPI3KPTENRasEGFR/ErbB2
(A) Erlotinib
A431Epidermoide0.420.210.145.51.9WTWTWTEGFR amp
HCC827NSCLC0.390.180.124.30.02NANANAEGFR E746–750 del
NCI-H292NSCLC0.440.310.285.20.5WTWTWTWT
NCI-H358NSCLC0.440.190.0813.54.4WTWTK-Ras G12CWT
NCI-H23NSCLC0.320.460.6814.124.9WTWTK-Ras G12CWT
NCI-H1299NSCLC0.280.310.5227.021.1WTWTN-Ras Q61KWT
Calu-6NSCLC0.490.250.1328.635.6WTWTK-Ras Q61KWT
NCI-H460NSCLC0.340.230.173.419.9PIK3CA E545KWTK-Ras Q61HWT
(B) Lapatinib
HCC70Breast0.460.280.200.33.2WTF90 fsWTWT
MDA-MB-468Breast0.420.250.162.64.5WTA72 fsWTWT
SK-BR-3Breast0.430.190.090.10.03WTNAWTNA
HCC1954Breast0.180.130.112.95.5PIK3CA H1047RWTWTWT
SK-OV-3Ovarian0.070.130.255.1>10PIK3CA H1047RWTWTErbB2 amp
NCI-N87Gastric0.450.550.691.60.04WTWTWTErbB2 amp

NOTE: Cells were simultaneously treated for 72 h with MK-2206 and erlotinib or lapatinib at constant concentration ratios spanning the IC50 dose of each agent. The evaluation of cell growth inhibitory effects was done by monitoring the cellular ATP concentration as described in Materials and Methods. CI values were calculated by the Chou and Talalay method for drug interactions using Calcusyn software for the different fractions affected (the CI values at ED50, ED75, and ED90 were summarized). Mutation data were from the COSMIC database or reference article (47).

Abbreviations: NA, not available; amp, amplification; del, deletion; fs, frame shift.