Figure 8. The combination of AZD1775 and Vorinostat suppresses tumor growth in a murine xenograft model and prolongs animal survival.

NOD/SCID-gamma (NSG) mice were subcutaneously inoculated in the right rear flank with 5×10⁶ U937 cells stably expressing luciferase. Treatment was initiated after luciferase activity was detected (5 days after injection of tumor cells). AZD1775 was freshly reconstituted with 0.5% methylcellulose and administrated at a dose of 50 mg/kg by oral gavage (p.o.) bid three days a week. Vorinostat in DMSO was diluted in PEG/H2O (1:1) and administrated at a dose of 100 mg/kg via intraperitoneal (i.p.) injection daily five days a week. Control animals were administered equal volumes of vehicle. (a) Tumor size was measured visually every other day. Representative median tumor volume for day 21 was shown. (b) Tumor growth was monitored every other day after i.p. injection with 150 mg/kg luciferin using the IVIS 200 imaging system. d = day. (c) Representative images of mice (day 21) and tumors removed from mice on the indicated day post-tumor cell injection. 1 = vehicle, 2 = 100 mg/kg Vorinostat, 3 = 50 mg/kg AZD1775, 4 = AZD1775 + Vorinostat. (d) Kaplan-Meier analysis performed to analyze survival of animals. Inset, median survival. (e) Tumor tissues were homogenized and subjected to Western blot analysis.