Figure 6

Ponatinib potently abrogates the growth of imatinib-resistant neoplastic cells expressing T674I FIP1L1-PDGFRα in nude mouse xenografts. (A) BALB/c nu/nu nude mice were subcutaneously inoculated with BaF3-T674I FIP1L1-PDGFRα cells, then randomized into 3 groups (10 animals each) for daily oral administration of vehicle [30% Cremophor EL/ethanol (4:1), 70% PBS], imatinib or ponatinib during days 5–21 after inoculation of cells. The tumor growth curves are plotted. Error bars represent 95% confidence intervals. (B) Dissected tumor xenografts were measured on day 21. ***, P < 0.0001, one-way ANOVA, post hoc comparisons, Tukey’s test. Columns, mean; error bars, 95% confidence intervals. Representative tumors removed from mice of each group are shown (upper). (C) Immnunohistochemical analysis with anti-Ki67 and H & E staining of xenograft tissues from mice sacrificed 21 days after tumor inoculation. (D) The signaling of PDGFRα in tumor tissue was inhibited by ponatinib. Whole cell lysates prepared from xenografts of each group were detected by immunoblotting with the indicated antibodies.