A. In SK-N-BE(2) xenografts, positive immunostaining for Y2R was detected in tumor cells and endothelium within tumor vasculature.
B. SK-N-BE(2) or SK-N-AS cells were subcutaneously injected into nude mice (n = 8–10). Daily injections of Y2R antagonists (100μl of 10−6M in saline) were initiated either 1 day after tumor cell inoculation and continued for 6 weeks (left panel) or started 10–14 days after cell inoculation and continued until day 22 (middle and right panels). In all experiments, Y2R antagonist significantly inhibited xenograft growth.
C. In SK-N-BE(2) xenografts, the Y2R antagonist significantly decreased tumor cell proliferation and increased apoptosis, measured as an area of Ki67 or TUNEL staining.
D. In SK-N-AS tumors, Y2R antagonist decreased levels of phosphorylated p44/42 MAPK (Western blot, representative samples shown).