Table 2.

Synergistic inhibition of cell proliferation by the combination of MK-2206 and docetaxel in breast cancer cell lines

Cell lineCombination indexDefects
ED50ED75ED90PI3KPTENRas
(A) Sequence dependency
BT-474PIK3CA K111NWTWT
    (i) MK-2206 followed by docetaxel1.61.51.6
    (ii) Simultaneous1.00.80.7
    (iii) Docetaxel followed by MK-22060.80.50.3
(B) Other cell lines
ZR-75-10.10.20.4WTL108RWT
MDA-MB-4531.20.60.3PIK3CA H1047RE307KWT
BT-201.00.70.5PIK3CA H1047RWTWT
MCF70.70.50.3PIK3CA E545KWTWT
HCC700.90.70.5WTF90 fsWT
MDA-MB-2310.90.70.7WTWTB-Raf G464V, K-Ras G13D
MDA-MB-4680.90.80.9WTA72 fsWT
SK-BR-30.80.70.8WTNAWT

NOTE: Cells were treated with MK-2206 and docetaxel 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).