Figure 7.

Cabozantinib inhibits FLT3-ITD signaling in MV4-11-R cells and growth of MV4-11-R-derived tumors. Kinase phosphorylation of the FLT3-ITD signaling pathway in cultured MV4-11-R cells was evaluated by Western blot analysis (A). MV4-11-R tumor xenografts were grown in nude mice; when tumor sizes reached 100–200 mm³, mice were then given 30 mg/kg of cabozantinib-malate in a single dose. Mice were sacrificed after 4 h or 24 h, and protein extracts were prepared from the tumor tissues and analyzed by Western blotting (B). To assess tumor growth, mice with MV4-11-R xenograft tumors reaching 100–200 mm³ were randomly given vehicle, 10 mg/kg, or 30 mg/kg cabozantinib-malate daily in four five-day courses (days 1–5, 7–11, 13–17, and 19–23). Tumor volumes were measured every 1–2 days (C), and Kaplan–Meier survival curves of the different mice groups were plotted against the number of days after treatment (D). Multiple tumors from each treatment group were obtained, weighed (E), stained with hematoxylin and eosin (H&E) or Ki-67 antibodies, and quantified for the number of Ki-67-positive cells (F). Quantification data represents the mean ± SD from three independent experiments. *, p < 0.05; **, p < 0.01; ***, p < 0.001. Scale bars = 200 μM.