Fig. 9
NRPa-308 decreases experimental ccRCC growth in a reverse dose-dependent manner. a Experimental tumors in nude mice (5 mice per condition) were obtained after injection of 3 × 106 786-O cells. Three concentrations of NRPa-308 (5 μg/kg, 500 μg/kg and 50 mg/kg) diluted in carboxymethyl cellulose, were given trice a week by oral gavage. The control group (Ctrl) received carboxymethyl cellulose. Tumor volume represented as a fold increase from the beginning of the treatment is presented. b Experimental tumors in immunocompetent mice (Balb-C, 5 mice per condition) were obtained after injection of 3 × 105 RENCA cells. Treatment (NRPa-308) was given trice a week by oral gavage. Two concentrations of NRPa-308- (5 μg/kg and 50 mg/kg) diluted in carboxymethyl cellulose were administered. The control group (Ctrl) received carboxymethyl cellulose. Tumor volume represented as the fold increase from the beginning of the treatment is shown. The tumor vasculature in each experimental group was detected by immuno-staining for CD31 (endothelial cells, green) and α-SMA (pericytes, cancer associated fibroblasts), red). Tumor sections were counterstained with 40,6-diamidino-2-phenylindole (DAPI) (nucleus, blue). c Quantification of the blood vessels (CD31 labeling). d Quantification of pericytes and cancer associated fibroblasts (α-SMA). e Quantification of blood vessels covered with pericytes (yellow labeling). f Representative images of the dose-dependent decrease in blood vessels covered with pericytes. *p < 0.05; **p < 0.01; *** p < 0.001