Abstract
5-Fluorouracil (5-FU) has been used as a chemotherapeutic drug for various types of cancer, although the development of resistance remains a major limitation for its use in clinical settings. In the present study, the anti-angiogenic effects of resveratrol and 5-FU either alone or in combination were examined in a B16 murine melanoma model. Co-treatment using resveratrol and 5-FU inhibited cell proliferation more efficiently compared with use of either drug alone and the antiproliferative effect coincided with changes in the expression levels of AMP-activated protein kinase (AMPK), cyclooxygenase-2, vasodilator-stimulated phosphoprotein (VASP) and vascular endothelial growth factor (VEGF). Furthermore, co-treatment with resveratrol and 5-FU reduced tumor growth compared with that in the control group and this growth-inhibitory effect was associated with changes in the expression levels of AMPK, VASP and VEGF. Immunohistochemical staining for angiogenesis demonstrated that co-treatment with resveratrol and 5-FU reduced the number of microvascular vessels compared with that in the control group. These results suggested that co-treatment with resveratrol and 5-FU suppressed cell growth and angiogenesis in B16 murine melanoma tumors.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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AMP-Activated Protein Kinases / metabolism
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Angiogenesis Inhibitors / administration & dosage
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Angiogenesis Inhibitors / pharmacology*
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Animals
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Antimetabolites, Antineoplastic / administration & dosage
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Antimetabolites, Antineoplastic / pharmacology*
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Antineoplastic Combined Chemotherapy Protocols / administration & dosage
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Antineoplastic Combined Chemotherapy Protocols / pharmacology
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Cell Adhesion Molecules / metabolism
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Cell Line, Tumor
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Fluorouracil / administration & dosage
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Fluorouracil / pharmacology*
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Melanoma, Experimental / blood supply*
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Melanoma, Experimental / drug therapy*
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Melanoma, Experimental / metabolism
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Melanoma, Experimental / pathology
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Mice
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Microfilament Proteins / metabolism
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Neovascularization, Pathologic / drug therapy*
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Neovascularization, Pathologic / metabolism
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Neovascularization, Pathologic / pathology
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Phosphoproteins / metabolism
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Resveratrol
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Stilbenes / administration & dosage
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Stilbenes / pharmacology*
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Vascular Endothelial Growth Factor A / metabolism
Substances
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Angiogenesis Inhibitors
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Antimetabolites, Antineoplastic
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Cell Adhesion Molecules
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Microfilament Proteins
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Phosphoproteins
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Stilbenes
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Vascular Endothelial Growth Factor A
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vasodilator-stimulated phosphoprotein
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AMP-Activated Protein Kinases
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Resveratrol
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Fluorouracil