Combined MEKi/STAT3i treatment improves survival of PKT mice. For survival study, PKT mice were treated with vehicle, AZD1480 (30 mg/kg/day), AZD6244 (25 mg/kg/day) or combined AZD1480/AZD6244 by oral gavage 5 days/week, starting at 4 weeks of age. A, tumor weight in the AZD1480/AZD6244 treated mice was significantly decreased compared with vehicle-treated controls. B, Kaplan-Meier survival analysis shows significantly improved overall survival with AZD1480/AZD6244 (median 85 days) compared with vehicle control (median 53 days, p=0.0002, log-rank test). C, Western blot analysis of whole tumor lysates demonstrated decreased expression of pSTAT3 and pERK in mice treated with AZD1480/AZD6244 compared to vehicle or single drug treated mice (left panels) and analyzed using Image J (right panels). D, Proliferation (Ki67 staining) was significantly decreased and apoptosis (cl caspase 3) (E) was significantly increased with AZD1480/AZD6244 treatment when compared to either vehicle or AZD6244 treated mice. F, AREG amount was significantly decreased in the serum of AZD1480/AZD6244 treated mice when compared to either AZD1480 or AZD6244 treated mice. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001; ns, P > 0.05.