Figure 5

Targeting the actin cytoskeleton overcomes resistance to HDACi in HMCL. Graphs representing proportion of cell death induced in HMCL treated with a combination of HDACi – LBH589 (0, 5, 10 and 20 nM) and MEK/ERK (GSK1120212 or ARRY-162, at 0.5 and 1 μM, respectively), FAK inhibitors (TAE226 and PF50638, both at 0.5 μM) or PI3K inhibitors (GDC-0941 or BKM120, both at 0.5 μM) for 72 h estimated through flow cytometric enumeration of propidium iodide staining. (a) HDACi-resistant cell line U266 was treated with inhibitors (LBH589 at 0, 5, 10 and 20 nM) as above and proportion of cell death is shown. (b) HDACi-resistant cell line OPM2 was treated with inhibitors (LBH589 at 0, 1, 5 and 10 nM) as above and proportion of cell death is shown. (c) HDACi-intermediate cell line RPMI-8226 was treated with inhibitors (LBH589 at 0, 1, 5 and 10 nM) as above and proportion of cell death is shown. (d) HDACi-sensitive cell line OCI-MY1 was treated with inhibitors (LBH589 at 0, 1, 5 and 10 nM) as above and proportion of cell death is shown. Each point represents mean±S.E.M. of the proportion of cell death from three individual experiments. Synergistic combinations were determined through two-way ANOVA analysis and significances are as indicated (α – P<0.05, LBH589 versus LBH589+GSK1120212; β – P<0.05, LBH589 versus LBH589+ARRY-162; χ – P<0.05, LBH589 versus LBH589+TAE226; δ – P<0.05, LBH589 versus LBH589+PF50638; ɛ – P<0.05, LBH589 versus LBH589+GDC-0941, φ – P<0.05, LBH589 versus LBH589+BKM120)