Figure 7. Pertuzumab increases MEK inhibitor efficacy in vitro and in vivo in WT/WT melanoma.
A) CHL1 and Bowes cells were treated for 48 hr with increasing concentrations of GSK’212 (10, 25, 50, 100 and 500 nM). Cells were lysed and lysates Western blotted, as indicated (upper panel). Cells were plated at clonal density and treated as indicated. Medium and GSK’212 were replaced after 3 days. After 6 days cells were fixed and stained with crystal violet (lower panel). Crystal violet was quantified using Image J. *P<0.05, **P<0.01. Scale bars represent 50 μm. Graphed is the mean intensity from 3 independent experiments. B) Cells were treated with GSK’212 (50 nM) alone, pertuzumab (1 μg/ml) alone or in combination. Medium and treatments were replaced after 3 days. After a further 3 days, cells were fixed and stained with crystal violet. *P<0.05, **P<0.01. Scale bars represent 50 μm. Graphed is the mean intensity from 3 independent experiments. C) Graph representing average tumor volume −/+ SEM in CHL-1 xenografts in nude mice treated either with vehicle, pertuzumab alone (200 μg/mouse), MEK inhibitor alone (PD0325901 chow at 7 mg/kg), or pertuzumab in combination with PD0325901 (combo); pertuzumab was administered intraperitoneally every 3 days. *P<0.05, pertuzumab alone vs combo; ###P<0.001 MEK inhibitor alone vs combo.