Figure 6. AZD6738 induces DNA damage, apoptosis, and exhibits anti-tumor efficacy in xenograft models of high-risk medulloblastoma and neuroblastoma in vivo.
(A–B) Tumor volumes over time of nude mice harboring IMR5 (A) and HD-MB03 (B) subcutaneously xenografted tumors treated with AZD6738 by oral gavage at 50 mg/kg body weight/day (red) or as compared to vehicle control (blue). Asterisks denote p < 0.05. Error bars represent standard deviations of 10 individual xenograft mice per group. Arrows denote start of treatment. (C) Representative photomicrographs of sections from IMR5 (top) or HD-MB03 (bottom) tumors upon completion of treatment with AZD6738 (50 mg/kg/day) or vehicle control in vivo, and stained for hematoxylin and eosin H&E, Ki67, cleaved caspase-3, and H2AX, as indicated. Scale bar = 100 μm. (D–F) Quantification of the number of cells positively stained for Ki67 (D), cleaved caspase-3 (E) and H2AX (F) in IMR5 or HD-MB03 xenograft tumors upon completion of treatment with AZD6738 (50 mg/kg/day, red) or vehicle control (blue) in vivo. *p = 3.1 x 10−5 and 0.001 for Ki67 in AZD6738 versus vehicle-treated IMR5 and HD-MB03, respectively. *p = 0.001 and 4.9 x 10−4 for cleaved caspase-3 in AZD6738 versus vehicle-treated IMR5 and HD-MB03, respectively. *p = 0.014 and 4.3 x 10−4 for H2AX in AZD6738 versus vehicle-treated IMR5 and HD-MB03, respectively. Error bars represent standard deviations of 3 independent fields analyzed.