Figure 1

Effect of fibroblast growth factor receptor (FGFR) and phosphatidyl inositol 3'kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitors on signaling and tumor outgrowth. T1 (A) or 67NR (B) cell cultures were treated for 1 hr with 0.5 μM NVP-BEZ235 or control dimethyl sulfoxide (DMSO)-containing medium, lysates were prepared and a western analysis for the indicated proteins and phospho-proteins was performed. (C) Starting 7 days after injection of 4T1 cells in mammary fat pads, groups of tumor-bearing mice (n = 6) were treated for 14 days with vehicle (PEG300), dovitinib (TKI, 20 mg/kg), NVP-BEZ235 (10 mg/kg) or a combination of both, and tumor volume was determined; representative of two different experiments. (D) 4T1 tumor-bearing mice were treated with a single dose of the vehicle (PEG300), dovitinib (TKI, 20 mg/kg), NVP-BEZ235 (10 mg/kg) or a combination of both (TKI + BEZ) and sacrificed 2 hrs later. Tumor lysates were prepared from three independent mice per group and a western analysis for the indicated proteins and phospho-proteins (P) was performed. (E) Quantification of metastatic foci number in the lung tissue taken from animals at the end of the experiment in panel C. N = 6, representative of two separate experiments. *P < 0.05 **P < 0.01 (Mann-Whitney U-test).