Resveratrol suppresses the angiogenesis and tumor growth of gliomas in rats.
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.
Tseng
Sheng-Hong
SH
Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Lin
Swei-Ming
SM
Chen
Jin-Cherng
JC
Su
Yen-Hao
YH
Huang
Hsin-Yi
HY
Chen
Chia-Kang
CK
Lin
Po-Yin
PY
Chen
Yun
Y
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
D020533:Angiogenesis Inhibitors; D013267:Stilbenes; D000077185:Resveratrol