SCC244 significantly inhibited c-Met–driven tumor growth in cancer CDX models. SCC244 significantly inhibited c-Met–driven tumor growth in cancer CDX models.

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SCC244 significantly inhibited c-Met–driven tumor growth in cancer CDX models. SCC244 significantly inhibited c-Met–driven tumor growth in cancer CDX models. A, SCC244 inhibits tumor growth in MKN-45, SNU-5, and EBC-1 xenografts. SCC244 was administered orally once daily after the tumor volume reached 100 to 200 mm3. Tumor volumes were measured twice a week and are shown as the mean ± SE. Significant difference from the vehicle group was determined using a t test. **, P < 0.01; ***, P < 0.001. B, An IHC evaluation of Ki67 expression was determined in the EBC-1 and SNU-5 xenograft models 2 hours after the final administration of SCC244 (scale bars, 100 μm). C, SCC244 reduced secretion of human IL8 in the EBC-1 and SNU-5 xenograft models. Serum levels of human IL8 were determined by ELISA of EBC-1 and SNU-5 xenografts on day 21. ***, P < 0.001 versus vehicle group, as determined using a t test. D, Mice bearing EBC-1 subcutaneous tumor xenografts were orally administered 2.5 or 10 mg/kg SCC244 only once. Tumors were harvested at several time points, p-c-Met, p-AKT, and p-ERK in tumor samples were detected by immunoblotting, and relative phosphorylation was calculated as described in Materials and Methods and are presented as the mean ± SD. Jing Ai et al. Mol Cancer Ther 2018;17:751-762 ©2018 by American Association for Cancer Research