Abstract | OBJECTIVE: METHODS:
SI-27 was applied at noncytotoxic concentrations (1-100 micromol/L), and its effect on nonmitogenic vascular endothelial growth factor ( VEGF)-enhanced cell motility and in vitro angiogenesis by human umbilical vein endothelial cells was determined. The activity of MMP-1, MMP-2, and tissue inhibitor of metalloproteinase 1 was determined by enzyme-linked immunosorbent assay. The effect of SI-27 on in vitro angiogenesis stimulated by supernatants of human glioma cell lines (U87MG, U251MG, and U373MG) also was examined. Angiogenesis was detected with variable vacuum scanning electron microscopy. RESULTS: Cell motility and in vitro angiogenesis by human umbilical vein endothelial cells were significantly increased by VEGF. The maximal effect on cell motility by VEGF was noted at 5 ng/ml (P < 0.001), and the maximal effect on the capillary network was observed at 10 ng/ml (P < 0.001), along with elevated MMP-1 and MMP-2 activity. Whereas SI-27 significantly suppressed VEGF-mediated in vitro angiogenesis (50 micromol/L; P < 0.001) and inactivated both MMP-1 and MMP-2, the expression of tissue inhibitor of metalloproteinase 1 and VEGF-mediated cell motility were not affected by SI-27. The angiogenesis promoted by glioma supernatants showed a significant reduction in the presence of SI-27 (10 micromol/L; U87MG, P < 0.01; U251MG, P < 0.01; U373MG, P < 0.01). CONCLUSION:
SI-27 inhibited in vitro tumor angiogenesis by suppression of MMP. This agent may be anticipated to prevent tumor growth through an angiosuppressive effect.
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Authors | Daizo Yoshida, Masahiro Noha, Kunihiro Watanabe, Yuichi Sugisaki, Akira Teramoto |
Journal | Neurosurgery
(Neurosurgery)
Vol. 50
Issue 3
Pg. 578-86; discussion 586-8
(Mar 2002)
ISSN: 0148-396X [Print] United States |
PMID | 11841727
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Endothelial Growth Factors
- Lymphokines
- Matrix Metalloproteinase Inhibitors
- Oligopeptides
- Protease Inhibitors
- SI 27
- Tissue Inhibitor of Metalloproteinases
- Vascular Endothelial Growth Factor A
- Vascular Endothelial Growth Factors
- Matrix Metalloproteinases
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Topics |
- Cell Division
(drug effects)
- Cell Movement
(drug effects)
- Cells, Cultured
- Endothelial Growth Factors
(metabolism, pharmacology)
- Endothelium, Vascular
(cytology, drug effects, metabolism)
- Enzyme-Linked Immunosorbent Assay
- Glioma
(blood supply, ultrastructure)
- Humans
- Lymphokines
(metabolism, pharmacology)
- Matrix Metalloproteinase Inhibitors
- Matrix Metalloproteinases
(metabolism)
- Microscopy, Electron, Scanning
- Neovascularization, Pathologic
(prevention & control)
- Oligopeptides
(pharmacology)
- Protease Inhibitors
(pharmacology)
- Tissue Inhibitor of Metalloproteinases
(metabolism)
- Tumor Cells, Cultured
(drug effects)
- Vascular Endothelial Growth Factor A
- Vascular Endothelial Growth Factors
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