Fig. 4. Significant tumour growth and angiogenesis inhibition upon treatment of orthotopic HT29 and HT29 VEGF-A knockout (VEGF-A KO HT29) tumour-bearing mice with Y2R antagonists, BIIE0246 and JNJ5207787.

a HT29 tumour weight was significantly lower in the Y2R antagonists, BIIE0246 and JNJ5207787 treated groups compared to untreated control. n = 11 per group. b Representative IHC images and graphical representation of the number of CD31 + ve vessels in ten high-power microscopic fields (HPF) showed that angiogenesis was also significantly reduced in HT29 tumours upon treatment with Y2R antagonists. n = 11 per group; data represent the summary of six or more sections per mouse from each group. c In situ tunnel assay showed a significant increase in tumour cell apoptosis in HT29 tumours upon treatment with Y2R antagonists; data represent the summary of 6 or more sections per mouse from each group. d Representative images of IHC showed that both NPY and Y2R are overexpressed in HT29 KO VEGF-A tumours. n = 11 per group; data represent the summary of six or more sections per mouse from each group. e IHC and graphical representation of the number of CD31 + ve vessels in ten high-power microscopic fields (HPF) indicated that VEGF-A KO HT29 control tumours are highly angiogenic, and angiogenesis is significantly reduced in VEGF-A KO HT29 tumours upon treatment with Y2R antagonists, BIIE0246 and JNJ5207787. f Correlation between NPY IHC score and CD31 counts in VEGF-A KO HT29 tumours (r² = 0.5994). g Treatment of orthotopic HT29 KO VEGF-A tumour-bearing mice with Y2R antagonists, BIIE0246 and JNJ5207787, significantly reduced tumour weight. h In situ tunnel assay showed a significant increase in tumour cell apoptosis in HT29 KO VEGF-A tumours upon treatment with Y2R antagonists. Results are expressed as mean ± SEM; *P < 0.01 compared to untreated control. Scale bar, 100 μm.