Figure 3. Identification of cells that are sensitive to FAK and HDAC inhibitor combinations.
A, Nuclei counts of A549 (left) and Flo1 (right) cells following treatment with vorinostat (5 μM), panobinostat (7.5 nM), and VS-4718 (500 nM) for 24 hours. Data are normalized to DMSO values and are displayed as mean ± SEM (n = 2 independent experiments). *, P < 0.05; **, P < 0.01; ***, P < 0.001 (two-way ANOVA). B, Combined inhibition of FAK and HDAC blocks colony formation. Representative images are shown (top). Bar charts (bottom) are plotted as means ± SEM (n ≥ 3 independent experiments). C, Combination of FAK and HDAC inhibition reduces cell viability. Dose matrices of viability of A549 (top) and Flo1 (bottom) cells following treatment with vorinostat (μM; left) or panobinostat (nM; right). D, Cell cycle distribution in A549 (left) and Flo1 (right) cells following treatment with the same drugs as used in B for 24 hours. Results in C and D are displayed as means (n ≥ 3 independent experiments). E, FAK and HDAC inhibition enhances the induction of apoptosis in A549 (left) and Flo1 (right) cells. Bar charts are plotted as means ± SEM (n ≥ 3 independent experiments). F, Combination of panobinostat and VS-4718 inhibits A549 (left) or Flo1 (right) tumor growth. Tumor volumes are plotted as means ± SEM [n ≥ 4 mice per group (2 tumors per mouse)]. Mice were treated from day 0 and accompanying body weights are shown (mean ± SD). For B, E, and F, *, P < 0.05; **, P < 0.01; ***, P < 0.001 (one-way ANOVA).