Fig. 2

Effects of simultaneous RAF and MEK inhibition in different genetic contexts. a and c RAS-mut lung (A549, KRAS-mut, and NCI-H1299, NRAS-mut) and pancreatic (MiaPaCa2 and HPAFII, both KRAS-mut) cells were exposed to increasing concentrations of trametinib (0.01–10 nM) and either BRAF inhibitor dabrafenib (0.01–10 μM) or the Pan-RAF inhibitor RAF265 (0.1–10 μM); combination experiments were performed using fixed ratio 1:1000. Cells were exposed to treatments for 72 h and cell viability was assessed by Crystal violet assay. The results represent the average ± SD of three independent experiments. b and d CI were calculated by conservative isobologram analysis for experimental data by this method, an average CI at the ED₅₀, ED₇₅, and ED₉₀ < 1 indicates synergism, =1 indicates additivity, and > 1 indicates antagonism. Isobologram graphs were obtained plotted CI against the fraction affected. Asterisks indicate statistically significant differences (p < 0.05 by 2-tailed Student’s t test) for the comparison between * combination- and dabrafenib-treated cells or ** combination- and trametinib-treated cells