Resveratrol Suppresses the Angiogenesis and Tumor Growth of Gliomas in Rats
Journal
Clinical Cancer Research
Journal Volume
10
Journal Issue
6
Pages
2190-2202
Date Issued
2004
Author(s)
Abstract
Purpose: We wanted to investigate the antitumor effects and effect on angiogenesis of resveratrol in rat RT-2 gliomas. Experimental 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 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.
SDGs
Other Subjects
resveratrol; animal cell; animal experiment; animal model; animal tissue; antigen expression; antineoplastic activity; article; cancer inhibition; cell proliferation; cell sorter; concentration response; controlled study; cytotoxicity; drug activity; drug effect; flow cytometry; glioma; glioma cell; growth inhibition; growth rate; human; human cell; immunohistochemistry; in vitro study; nonhuman; priority journal; protein expression; rat; survival rate; time; tumor growth; tumor volume; umbilical vein; Angiogenesis Inhibitors; Animals; Apoptosis; Cell Division; Cell Line; Cell Line, Tumor; Disease Models, Animal; Endothelium, Vascular; Flow Cytometry; Glioma; Kinetics; Neovascularization, Pathologic; Rats; Stilbenes; Umbilical Veins
Type
journal article