PD0325901 inhibits the growth of SKMEL-28 xenografts. A, mice with established SKMEL-28 xenografts were treated by p.o. gavage with PD0325901 (25 mg/kg five times weekly) for 8 wk or vehicle only as control. Selected mice were sacrificed after 1, 2, 3, 4, and 8 wk of treatment for molecular studies. After 8 wk, treatment was discontinued and tumors were then monitored for regrowth. Each line represents an individual mouse treated with either PD0325901 (blue solid lines) or the vehicle only (red dotted lines). B and C, PD0325901 treatment resulted in down-regulation of ERK activity, down-regulation of cyclin D1 expression, up-regulation of p27, and hypophosphorylation of Rb. These effects on MAPK pathway activity were accompanied by proliferative arrest as measured by Ki-67 staining (C) and an increase in the melanocyte differentiation marker tyrosinase (B). P-ERK, phosphorylated ERK; P-Rb, phosphorylated Rb.