In vivo inhibition of VEGF- and bFGF-induced angiogenesis by NS398 and piroxicam. (A-E) Histologic sections of Matrigel plugs after 9 days after implantation, and stained with Masson trichrome. bFGF (50 ng/mL; A) and VEGF (10 ng/mL; C) were used as angiogenic stimuli. NS-398 was injected daily at 3 mg/kg in mice bearing Matrigel plugs containing bFGF (B), or VEGF (D). Photographs were taken at × 150 original magnification. (E) High magnification (original magnification, × 300) of panel C, as indicated by the arrow. (F) The level of angiogenesis in the Matrigel plugs was determined by quantitation of the total number of erythrocytes contained in the Matrigel. The mean + SEM of 2 experiments are shown; *P < .001; **P < .05. (G) Inhibition of CXCR4 expression by NS-398 on murine endothelial cells. The in vivo experiments and the isolation of the endothelial cells were performed as described in “Materials and methods.” The dot plots indicate the MFI of CXCR4 (FL1) and VEGFR-2 (FL2). The percentage of CXCR4⁺ cells is indicated in each quadrant. The data represent one representative of 2 experiments.