Figure 4

AZD1152 inhibits orthotopically xenografted HER18 cells in nude mice. (A) Tumor growth curves for orthotopically implanted HER18 cells are shown. Control mice received vehicle (0.3 M Tris pH 9.0), low dose mice received 62.5 mg/kg/dose AZD1152, and high dose mice received 125 mg/kg/dose AZD1152. Treatment began when tumors were measurable (approximately 50 mm³). Injections were given IP on days 1 and 2 of 7-day cycles, indicated by horizontal bars just above the x-axis. * P < 0.001 calculated as a mixed linear model. Error bars represent SE. (B) Representative mice bearing xenografts (arrows) from each treatment group. (C) Weights of dissected xenografts are plotted as means for each treatment group. Error bars represent 95% confidence intervals. P values were determined by one-way ANOVA. (D) H&E stained control and high dose (125 mg/kg/day) tumor samples are shown. Multi-nucleate cells (circles) were observed in tumor sections from AZD1152-treated mice but not in control mice. (E) Western blots using anti-phospho-Histone H3 and anti-actin are shown as labeled. (F) Histology and immunohistochemistry of xenografts are shown: top panels- H&E staining; middle panels- immunohistochemistry with antibodies for Ki-67; lower panels- cleaved Caspase 3.