Fig. 3
Evaluation of type II MET-TKIs in Hs746t in vitro and in vivo models. A The IC50 values (nM) of each drug for Hs746t cells harboring METex14 plus the indicated MET secondary mutations are expressed according to the indicated color scale. Growth inhibition curves are summarized in Additional file 2: Fig. S3. B Western blot analyses of Hs746t cells with METex14 with/without D1228N secondary mutation treated with MET-TKIs at the indicated concentrations for 3 h. β-actin was used as a loading control. C Changes in tumor size in vivo. Clinical dose of foretinib and cabozantinib used in phase II trial or clinical practice was converted to equivalent dose in mice considering the body surface area (Nair AB, Jacob S. J Basic Clin Pharm. 2016). Tumor size was measured every 2 days. Tumor Volume (TV) was calculated as follows: TV (cm3) = length × width × width × 0.5. Statistical analysis was performed using the Kruskal–Wallis test with the Dunnett’s multiple comparison test. P < 0.05 was considered to indicate statistical significance (* means P < 0.05). D Comparison of resected tumors treated with each drug from sacrificed mice on day 10. E H&E-stained histopathological images and phosphorylated MET in resected tumors treated with each drug determined by immunohistochemistry are shown. F The change (%) in the average body weight of mice during the treatment is shown compared to body weight before treatment