title: Gamma-secretase inhibitor does not modulate angiogenesis in colon adenocarcinoma in obese mice.
abstract: BACKGROUND
  Notch is a signaling molecule which plays a role in angiogenesis and γ-secretase is required for processing of Notch. In this study, we investigated the effect of γ-secretase inhibitor (DAPT) on tumor angiogenesis in diet-induced obese mice.
  
  
  METHODS
  18 mice were divided into three groups; control, obese (diet-induced) and obese+DAPT. After 15 weeks, the obese mice were subjected for tumor induction of CT26 colon adenocarcinoma cells (5 x 105 cells). When the tumor size reached approximately 350 ± 50 mm3, half of the obese animals received DAPT (10mg/kg/day) subcutaneously. Blood samples were taken after 14 days and the tumors harvested for immunohistochemical staining and capillary density were reported as CD31 positive cells/mm2.
  
  
  RESULTS
  The obese animals had higher serum leptin and NO concentrations, while, serum VEGF and VEGFR-1 concentrations were not different compare to control group. Administration of DAPT in obese mice significantly reduced serum VEGFR-1 and leptin concentrations and increased serum NO level (p < 0.05). Capillary density in the tumors of obese animals was not different compare to control groups. DAPT administration could not alter capillary density in the tumors.
  
  
  CONCLUSIONS
  Administration of DAPT in obese mice altered serum angiogenic factors, however, it could not modulate tumor angiogenesis in diet-induced obese mice (Fig. 4, Ref. 26).
authors.forename: M
authors.initials: M
authors.lastname: Khazaei
authors.forename: E
authors.initials: E
authors.lastname: Kalantari
authors.forename: H
authors.initials: H
authors.lastname: Saeidi
authors.forename: N
authors.initials: N
authors.lastname: ShabaniKia
authors.forename: Z
authors.initials: Z
authors.lastname: Tahergorabi
authors.forename: B
authors.initials: B
authors.lastname: Rashidi
authors.forename: N
authors.initials: N
authors.lastname: Dana
authors.forename: S H
authors.initials: SH
authors.lastname: Javanmard
mesh_terms: D000230:Adenocarcinoma / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D000818:Animals; D003110:Colonic Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D004151:Dipeptides / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008820:Mice, Obese; D009374:Neoplasms, Experimental / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D009765:Obesity / Q000150:complications* / Q000378:metabolism / Q000473:pathology
chemical_list: D004151:Dipeptides; C419410:N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester; D053829:Amyloid Precursor Protein Secretases
keywords: adenocarcinoma.; angiogenesis; obese; γ-secretase