title: Resveratrol suppresses the angiogenesis and tumor growth of gliomas in rats.
abstract: OBJECTIVE
  We wanted to investigate the antitumor effects and effect on angiogenesis of resveratrol in rat RT-2 gliomas.
  
  
  METHODS
  RT-2 glioma cells were treated with resveratrol, and then cytotoxicity was assayed, apoptosis was measured by flow-activated cell sorter flow cytometry, and expression of vascular endothelial growth factor was measured by reverse transcription-PCR. Tumor size, animal survival time, and survival rate were followed in resveratrol-treated rats with s.c. or intracerebral gliomas. Furthermore, in vitro proliferation was assayed to explore the effect of resveratrol on the proliferation of ECV304 human umbilical vein endothelial cells. Expression of CD31 in resveratrol-treated gliomas was followed immunohistochemically to study the effect of resveratrol on the glioma-induced angiogenesis.
  
  
  RESULTS
  Resveratrol was demonstrated to exert cytotoxic effects and induce glioma cell apoptosis in a concentration- and time-dependent manner (P < 0.05). Resveratrol (40 mg/kg/day) exerted significant antitumor effects on s.c. tumors, including slower tumor growth rate, longer animal survival time, and higher animal survival rate (P < 0.05). In contrast, resveratrol affected intracerebral tumors at only an increased dose (100 mg/kg/day), prolonging animal survival (P < 0.05) without affecting survival rate. The expression of vascular endothelial growth factor in the glioma cells and the proliferation of ECV304 cells were inhibited by resveratrol in a concentration-dependent manner. Immunohistochemical analyses showed that the s.c. gliomas from resveratrol-treated rats had fewer microvessel densities than did control rats (P < 0.01).
  
  
  CONCLUSIONS
  Resveratrol caused significant glioma cell cytotoxicity and apoptosis, exerted antitumor effects on the s.c. and intracerebral gliomas, and inhibited angiogenesis in s.c. gliomas. Thus, resveratrol might be considered a possible treatment strategy for gliomas.
authors.affiliation: Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Sheng-Hong
authors.initials: SH
authors.lastname: Tseng
authors.forename: Swei-Ming
authors.initials: SM
authors.lastname: Lin
authors.forename: Jin-Cherng
authors.initials: JC
authors.lastname: Chen
authors.forename: Yen-Hao
authors.initials: YH
authors.lastname: Su
authors.forename: Hsin-Yi
authors.initials: HY
authors.lastname: Huang
authors.forename: Chia-Kang
authors.initials: CK
authors.lastname: Chen
authors.forename: Po-Yin
authors.initials: PY
authors.lastname: Lin
authors.forename: Yun
authors.initials: Y
authors.lastname: Chen
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D005434:Flow Cytometry; D005910:Glioma / Q000098:blood supply* / Q000473:pathology*; D007700:Kinetics; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D051381:Rats; D000077185:Resveratrol; D013267:Stilbenes / Q000627:therapeutic use*; D014471:Umbilical Veins
chemical_list: D020533:Angiogenesis Inhibitors; D013267:Stilbenes; D000077185:Resveratrol