Effect of dovitinib, AEE788 or the combination of both on 4T1 and 67NR tumors. (A) Groups of 4T1 tumor-bearing mice (n = 6) were treated for 12 days with PEG300 (Vehicle), AEE788 (50 mg/kg) or a combination of dovitinib (TKI, 40 mg/kg) + AEE788. AEE788 was administered 3×/week; dovitinib daily, and tumor volume was determined; representative of two experiments. (B) Groups of 67NR tumor-bearing mice (n = 5) were treated with PEG300 (Vehicle), AEE788 (50 mg/kg) or a combination of dovitinib (TKI, 40 mg/kg) + AEE788. Treatment was performed through days 7 to 13 and days 18 to 23. Dovitinib and vehicle were dosed daily; AEE788 was administered on days 7, 9, 11 and 13, then on day 18, 20 and 22, and tumor volume was determined. (C) Quantification of the number of metastatic foci covering lungs of mice from the experiment in Panel A. N = 6, representative of two separate experiments. (D) 4T1 tumor-bearing mice were treated with PEG300, a single dose of AEE788 (50 mg/kg) or a combination of dovitinib (TKI, 40 mg/kg) + AEE788, then sacrificed 2 hrs later. Tumor lysates were prepared from three mice per group and a western analysis for the indicated proteins and phospho-proteins (P) was performed. *P < 0.05 (Mann-Whitney U-test).