Fig. 6

The S63845/SKI-606 regimen exhibits significant in vivo activity. a–e NOD/SCID-γ NSG mice (5 mice/group) were inoculated in the right flank with 1 × 10⁶ U937 cells. Treatment was initiated after 8 days. S63845 (25 mg/kg, twice a week, I.P.) ± SKI-606 (150 mg/kg, 5 days weekly, p.o.) were administrated weekly for 2 weeks. a Tumor size was monitored every other day. Mean tumor volume was calculated using the formula (1/2 × [length × width²]). b, c At day 21, tumors were harvested and weighed. d Mouse body weights were monitored every other day throughout the treatment period. P > 0.05. e Immunoblotting analysis was then performed to monitor expression of PARP, cleaved caspase-3 and γH2A.X. β-actin was assayed to ensure equivalent loading and transfer. f–i Mice (10 mice/group) were inoculated via tail vein with 5 × 10⁶ MV4-11 cells stably expressing luciferase. After signals were visible (e.g, 13 days after injection of tumor cells), S63845 (15 mg/kg, twice a week for two weeks, then adjusted to one time weekly for three weeks, I.P.) ± SKI-606 (150 mg/kg, 5 days weekly, p.o.) were administrated for 5 weeks. Control animals were administered equal volumes of vehicle. f Tumor burden was monitored every week after subcutaneous (sub-Q) injection with 150 mg/kg luciferin using the IVIS 200 imaging system. g Quantification of the luminescent signal. Data represents the means ± SD performed on all mice for each group. h Kaplan–Meier survival plot (P = 0.0452 and 0.0038 for the combination vs S63845 or SKI-606 alone, respectively, by log-rank test). i Mouse body weights during treatment (P > 0.05). CF, cleavage fragment. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001