Fig. 6

In vivo synergistic antitumor effect of domatinostat in combination with Gemcitabine plus Abraxane in PANC28 and PANC1 xenograft models. A-B. PANC28 and PANC1 cells were s.c. injected into athymic mice as described in the Materials and Methods. When established tumors were palpable, mice were treated with vehicles or domatinostat (20 mg/Kg 5 days/week, per os) alone and in combination with gemcitabine (weekly 25 mg/Kg, i.p.) and abraxane (weekly 20 mg/Kg, i.p.) (GT) for two weeks. Relative tumor volume curves are reported as mean ± SEM tumor volume measured at the indicated timing. C-D. Percent change in tumor volume average from first day of treatment (day 0) to the end of the study (day 32 for PANC28 xenograft and day 25 for PANC1 xenograft) for each treatment group compared to vehicles group (middle panels). E-F. Tumor growth delay (TGD), determined, in both PANC28 and PANC1 xenografts, as %TGD = [(T − C) /C] × 100, where T and C are the mean times expressed in days for the treated or control groups, respectively, to reach a defined tumor volume (see Materials and Methods). G. Expression of FOXM1 and γH2AX protein levels in lysates from three PANC1 xenograft tumor samples from each treatment group evaluated by WB. β-actin serves as control for equal protein loading. On the right, proteins quantification reported as mean ± SD for each treatment groups. H. Paraffin-embedded tissues were generated for each group for IHC analysis for β-Catenin as described in the Materials and Methods. Images were captured with a 20X (white scale bar: 200 μm) and 40X (white scale bar: 50 μm) objectives on a light microscope. Statistically significant results, obtained by 2-way ANOVA test, are reported (*** indicates P < 0.0005, ** indicates P < 0.005 and * indicates P < 0.05)