Resveratrol Suppresses the Angiogenesis and Tumor Growth of Gliomas in Rats

Rupase: We wanted to investigate the antitumor effects and effect on angiogenesis of resveratrol in rat RT-2 gliomas. Ejs,enenmental Design: 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 gliomainduced angiogenesis. Rerub: Resveratrol was demonstrated to exert cytotoxic effects and induce glioma cell apoptosis in a concentrationand timedependent manner (P < 0.05). Resveratrol (40 mg/kg/day) exerted significant antitumor effects on s.c. tumors, including slower tumor growth rate, longer animal sunival time, and higher animal survival rate (P < 0.05). J~I 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 E C V W cells were inhibited by resveratrol in a concentration-dependent manner. Immunohistochemical analyses showed that the s.c. gliomas from Received 8/28/03; revised 1 1/18/03; accepted 11/21/03 . Grant support: Grant NTUH9 1 -SO40 from National Taiwan University Hospital and Grant NSC9 1-23 14-E3-002-338 from the National Science Council, Taiwan, Republic of China (S-H. Tseng). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Requests for reprints: Yun Chen, Department of Surgery, Far Eastern Memorial Hospital, 21, Sec. 2, Nan-Ya South Road, Pan-Chiao 220, Taipei 220, Taiwan. Phone: 886-2-29546200, ext. 2923, Fax: 886-2283 13781, E-mail: [email protected]. resveratrol-treated rats had fewer microvessel densities than did control rats (P < 0.01). Condusim: 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.