Fig. 5: MK-8776/olaparib combination reduces tumor growth in subcutaneous and orthotopic mouse models of neuroblastoma.

A WB analysis of tumor lysates explanted from IMR-32 xenografts intraperitoneally injected with vehicle (CTR), olaparib (Ola), MK-8776 (MK) and their combination (MK + Ola) for 30 h (n = 3/group). Blots were probed with the indicated antibodies and β-actin was used as loading control. The asterisk indicates the 89 kDa PARP1 cleaved fragment. B Bar plot representing the ratio between cleaved versus full length PARP1 expression assessed by densitometry (means ± SD) of the WB in (5A). C Tumors explanted from IMR-32 xenografts after 2 weeks (n = 3/group). D Representative images of IHC analysis with the indicated antibodies in tumor samples explanted after 5 days of treatment; magnification (×132). Scale bar: 200 µm. E Mean counts of γH2AX, cleaved caspase 3 and CD31 positive cells detected on four high power fields (HPF) for each of four biological replicates/group. nd not determined. F Evaluation of tumor growth in IMR-32 xenograft treated as above for 2 weeks; data were expressed as mean volume + SEM (n = 7/group, Ola n = 6). G Evaluation of tumor growth in nude mice orthotopically inoculated with IMR-32-luc cells and treated as above for three weeks. Tumor growth was monitored by bio-luminescence imaging (BLI) at the indicated times. Plot representing the photon counts in the tumor region of interest (ROI). Data were reported as mean + SEM (n = 10/group). For all experiments p values were calculated by ANOVA (*p < 0.05, **p < 0.01, ***p < 0.001).