Fibroblast growth factor receptor 3 (FGFR3) inhibition cooperated with MEK inhibition to inhibit tumor growth in orthotopic xenograft mice. A, Primary tumor growth of Cal27 cells in xenograft mice injected with the indicated inhibitors. Cal27 cells were injected s.c. into the tongues of nude mice (n = 4/group). The mice were treated twice per week for 28 d by i.p. injection with DMSO (vehicle control), 20 mg/(kg day) AZD6244, 10 mg/(kg day) PD173074, or 10 mg/(kg day) PD173074 at 1 d post‐injection of 20 mg/(kg day) AZD6244. B, In vivo imaging system (IVIS) images of tumors in the tongue at 52 d post‐injection. The tumor was detected by in vivo fluorescence imaging analysis, as described in Materials and Methods. C, Tumor volumes of mice (n = 4/group) were measured with a caliper on the indicated days. Each value represents mean ± SEM between replicates (n = 4/group). D, H&E staining of tumor tissue in a mouse model. Magnification, 40× or 100×. Scale bar = 100 μm or 60 μm. E, Ki67, phospho‐FGFR3, phospho‐Akt, phospho‐ERK, and cleaved caspase‐3 expression in tumor tissues were measured by immunohistochemistry. Magnification, 100×. Scale bar = 60 μm.