Fig. 2

The combination of trametinib and dexamethasone is synergistic and glucocorticoid receptor-dependent. a. A panel of multiple myeloma cell lines was exposed to a matrix of trametinib and dexamethasone for 5 d. Cell proliferation was assessed by CellTiter-Blue assay and synergy calculated using the Bliss independence model. Data are representative of 3 independent experiments carried out in triplicate. b. MM.1S, MM.1R, RPMI8226, JJN3 and L363 cell lines were exposed to DMSO, 30 nM trametinib, 100 dexamethasone or the combination of trametinib and dexamethasone for 5 d. Cells were fixed, stained for annexin V and analysed by flow-cytometry. The number of early and late apoptotic cells combined is expressed as a percentage of total cells. Data are representative of 3 independent experiments. c. MM.1S cells were treated with trametinib, dexamethasone or their combination and cumulative cell doublings determined by cell counting. Significance was determined by two-way Anova *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. Data are representative of 3 independent experiments. d. MM.1S cells were treated with DMSO, 30 nM trametinib, 100 nM dexamethasone or their combination for the indicated times and cell lysates analysed by Western blotting for the indicated proteins. Data are representative of 3 independent experiments. Blot images were cropped for clarity of presentation