Effect of Blocking of Neuropeptide Y Y2 Receptor on Tumor Angiogenesis and Progression in Normal and Diet-Induced Obese C57BL/6 Mice

Background: Obesity is a risk factor for some types of cancers. Angiogenesis is a necessary step in the multistage progression of tumors such as melanoma. Previous studies reported that neuropeptide Y (NPY) regulates angiogenesis by activating the Y2 receptor on endothelial cells. The present study examined the effects of the NPY Y2 receptor antagonist on tumor weight, angiogenesis and serum levels of vascular endothelial growth factor (VEGF), VEGF receptor-1 (VEGF-R1), and nitric oxide (NO).

Methods: Twenty four male C57BL/6 mice were divided into control and obese groups. The control group was fed a normal diet whereas the obese group was fed a high fat diet. After 16 weeks, 2 × 106 B16F10 melanoma cells were injected subcutaneously into all animals. Half of the control and the obese animals received 1 µM, 100 µL/kg NPY Y2 receptor antagonist (BIIE 0246) intraperitoneally. After two weeks, the animals were sacrificed, and angiogenic factors and tumor weights and angiogenesis were analyzed.

Results: Tumor weight in the obese mice was higher than in the control (p<0.05). Treatment with BIIE 0246 reduced tumor weight in the obese animals (p<0.05), without effect on control group (p>0.05). Administration of an NPY Y2 receptor antagonist decreased tumor angiogenesis (evaluated as capillary density/mm2) and serum VEGF concentration in the obese group without altering serum VEGF-R1 and NO concentrations.

Conclusions: Blockade of the NPY Y2 receptor suppressed tumor growth in obese mice by affecting tumor angiogenesis. Thus, it seems that NPY and its Y2 receptor antagonist might be new targets in melanoma tumor therapy.