Figure 6:

The effects of AZD4547 on radiation-induced xenograft tumor growth delay. Tumor growth delay curves of (A) NCI-H1581 and (C) NCI-H226 subcutaneous flank xenografts treated with vehicle, AZD4547 (6.26 mg/kg or 12.5 mg/kg), radiation (2 Gy × 5 or 2 Gy x10) or AZD4547 (6.25 mg/kg or 12.5 mg/kg) plus radiation (2 Gy × 5 or 2 Gy x10). AZD4547 was delivered as p.o. gavage at 1 h before radiation fraction. (B & D) Time from start of treatment for tumor volumes to triple. IHC analysis of (E) H1581 and (G) NCI-H226 tumor sections showing modulation of FGFR-downstream signaling (pMAPK and pS6) and apoptotic markers (CC3). pMAPK and pS6 analysis were conducted at 8 hours following a single dose of AZD4547 (6.25 mg/kg or 12.5 mg/kg), radiation (2 Gy) or AZD4547 plus radiation whereas CC3 data were collected at 48 hours post-treatment, respectively. (F and H) Percent staining for pMAPK, pS6 at 8 hours post treatment and number of CC3 positive cells after 48 hours of treatment. Each stain was objectively quantified in three high-powered fields for three independent tumors. No pMAPK expression was observed in the NCI-H1581 tumors. The scale bar represents 50 μm. Points, mean tumor volume in mice after treatment; bars, SEM, *, P < 0.05, according to one-way ANOVA.