Figure 5

From: Inhibition of Mcl-1 enhances cell death induced by the Bcl-2-selective inhibitor ABT-199 in acute myeloid leukemia cells

Figure 5

A-1210477 synergizes with ABT-199 in ABT-199-sensitive acute myeloid leukemia (AML) cells. (a) MOLM-13 cells were treated with ABT-199 and A-1210477, alone or in combination, for 4 h and then subjected to annexin V/PI staining and flow cytometry analyses. ***P<0.001. Combination index (CI) values were calculated using CompuSyn software. (b, c) MOLM-13 cells were treated with ABT-199 and A-1210477, alone or in combination, for 4 h. Whole-cell lysates were subjected to western blotting and probed with the indicated antibodies. (d) Primary AML patient sample cells (AML#111–113) were treated with ABT-199 and A-1210477, alone or in combination, for 24 h and then subjected to annexin V/PI staining and flow cytometry analyses. ***P<0.001. CI values were calculated using CompuSyn software. (e, f) MTT analyses were performed on normal peripheral blood mononuclear cells (PMNCs) to determine proliferation inhibition at the indicated concentrations of A-1210477 and ABT-199, alone or in combination. Patient sample data are means of duplicates due to limited sample. Standard isobologram analyses of drug interactions were performed to determine the extent and direction of the drug interactions. The IC50 values of each drug are plotted on the axes; the solid line represents the additive effect, while the points represent the concentrations of each drug resulting in 50% inhibition of proliferation. Points falling below the line indicate synergism whereas those above the line indicate antagonism.