Fig. 5: Pharmacological inhibition of MEK5 or ERK5 impairs the proliferation of sarcoma cell lines and tumor growth.

Sarcoma cells were plated in 6-well dishes and, after 24 h, were treated with (a) BIX02189 or (b) JWG-071 at the indicated concentrations, and proliferation was quantified by cell counting after 4 or 3 days of treatment, respectively. The values were normalized to those in control cells (untreated) and are presented as the mean ± SD of two independent experiments with four biological replicates each. Statistical significance: **p ≤ 0.01; ***p ≤ 0.001. c Mice were implanted with GCT and (d) SJCRH30 cells. After engraftment, when the median volume of the tumors was ~150 mm3 (Day 11 for GCT or Day 9 for SJCRH30), the mice were treated with the ERK5 inhibitor JWG-071 or vehicle. Tumor progression was monitored every 2 days. Each point on the graph indicates the mean tumor volume ± SEM (left panels). Representative images of Ki67 and cleaved caspase-3 immunostaining in those tumors are shown at 40x magnification (middle panels). Expression was quantified in eight different images with ImageJ software and is presented as the percentage of positive cells relative to the total number of cells (right panels). The mean percentage (red dotted line) and p values are indicated: **p ≤ 0.01; ***p ≤ 0.001.