Figure 3. Activity of a MEK inhibitor in NF1-deleted sarcomas.

A) NF1-deleted cell lines (1863 and 3017) were exposed to either DMSO-alone or the MEK inhibitor PD325901 (50nM) for 7 days in culture. The number of colonies formed after 7 days was determined by crystal violet staining. B) Western blot showing inhibition of pERK levels following 4 hour exposure of 1863 cells to MEK inhibitor PD325901 (50nM). C) Primary high-grade myogenic sarcomas generated from intramuscular injection of Ad-Cre into NF1^flox/flox; Ink4a/Arf ^flox/flox mice were treated with vehicle alone or PD325901. Exposure to PD325901 slowed tumor growth in a majority of tumors, as showed on the left by the fold change in tumor volume following initiation of treatment. On right, a waterfall plot shows the absolute change in tumor volume for primary NF1-deleted myogenic sarcomas following vehicle or PD325901 treatment. For tumors that showed a partial response to treatment, the maximal percent loss in tumor volume is reported. For tumors that did not respond to treatment, the maximal percent gain in tumor volume is reported. D) Immunohistochemistry of pERK and pS6 levels in primary myogenic sarcomas that received vehicle-alone or PD325901. Tumors that responded to treatment show a decrease in pERK and pS6 levels compared to vehicle-alone tumors, whereas tumors that did not respond to treatment show a corresponding upregulation in both pERK and pS6 levels.