Figure 5.

Dual drug combinations of PKC-α, MET, and CDK6 inhibitors synergistically inhibit TNBC cell growth. (A) TNBC cells (MDA-MB-231, BT549, and Hs578T), non-TNBC cells (T47D and SK-BR-3), and normal epithelial cells (MCF10A) were used to determine the specificities of the cytotoxic effects of safingol (SA), crizotinib (Cr), and PD0332991 (PD) in dual-drug combinations. Cells (1x10³ to 3x10³) were plated in 96-well plates, and cell growth was determined by MTT assay 2 days after cells were treated with an inhibitor or a combination of inhibitors.(B) CI plots for the dual-drug combinations of inhibitors in six breast cancer cells lines. Cells were treated with combinations of safingol (0, 0.5, 1, 2, 3, 4, or 5 μM), crizotinib (0, 1, 2, 3, 4, 5, or 6 μM), and PD0332991 (0, 1, 2, 4, 6, 8, or 10 μM) for 48 hours. Open and closed symbols represent non-TNBC and TNBC cells, respectively. CI values were plotted as a function of fractional inhibition as determined by MTT analysis and computer simulation (CompuSyn) for the Fa (fraction affected) range of 0.10 to 0.95. CIs of <1, 1, and >1 indicate synergism, additive effect, and antagonism, respectively. At least three independent experiments with three replicates were performed.