Fig. 4
DNA methyltransferase inhibition effectively targeted MEKi resistant cells only. A, B Cell viability screen using inhibitors that target different epigenetic mechanisms in parental (A) or resistant cells (B). Dose response curves for cell line #3 determined after 72 h using the CellTiter-Glo® cell viability assay are shown. C The IC50 of DNMTi was significantly lower in six matched pairs of parental versus resistant cells (two-tailed paired Student’s t test). D, E Synergy analysis of MEKi plus DNMTi using the Loewe method of the Combenefit software shown for cell line #3 parental (D) and resistant (E). F Growth curves of PDX treated with MEKi, DNMTi or the combination. Solid lines represent the mean tumor volume of three mice per treatment group ± standard error of the mean (SEM). Statistical significance versus control was determined using a two-tailed unpaired Student’s t test