(A) H358 (5 × 106) cells were inoculated into the flank of nude mice on day −5, and the mice were treated with belinostat 40 mg/kg/mouse i.p. daily, trametinib (1 mg/kg p.o.daily), or in combination from day 1 to 22. The mice were sacrificed on day 22 and xenograft tumors were evaluated as described in Materials and Method. These data show the percent change in the tumor volume on day 22 relative to tumor at day 1. Bars indicating standard error are shown for groups of 12 mice where each symbol represents a single mouse for each of the groups. *, P < 0.05 for the combination compared with either belinostat alone or trametinib alone groups by one-way ANOVA. (B) The tumors were harvested on day 22 and examined for the indicated proteins by western blotting analysis. (C) Tumors harvested on day 22 were histologically examined. Sections were stained with H&E and probed with an anti-human FOXO3a monoclonal antibody. (D) Quantification of total FOXO3a positive nuclei. Columns, mean of five fields; bars, SD. *, P < 0.05 for the combination compared with either belinostat alone or trametinib alone groups by one-way ANOVA.