title: Effect of Blocking of Neuropeptide Y Y2 Receptor on Tumor Angiogenesis and Progression in Normal and Diet-Induced Obese C57BL/6 Mice.
abstract: 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, 2×10(6) 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.
authors.affiliation: . khazaeim@mums.ac.ir.
authors.forename: Masoud
authors.initials: M
authors.lastname: Alasvand
authors.forename: Bahman
authors.initials: B
authors.lastname: Rashidi
authors.forename: S H
authors.initials: SH
authors.lastname: Javanmard
authors.forename: Maziar Mohammad
authors.initials: MM
authors.lastname: Akhavan
authors.forename: Majid
authors.initials: M
authors.lastname: Khazaei
mesh_terms: D000818:Animals; D001835:Body Weight; D004195:Disease Models, Animal; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000453:epidemiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D009569:Nitric Oxide / Q000097:blood; D009765:Obesity / Q000453:epidemiology*; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000453:epidemiology; D047368:Tumor Burden; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood
chemical_list: D017476:Receptors, Neuropeptide Y; D042461:Vascular Endothelial Growth Factor A; C095889:neuropeptide Y2 receptor; D009569:Nitric Oxide; D040281:Vascular Endothelial Growth Factor Receptor-1