Suppression of cell invasion on human malignant glioma cell lines by a novel matrix-metalloproteinase inhibitor SI-27: in vitro study.
Matrix metalloproteinase (MMP) has come to be highlighted by its close relation to the cell invasion of gliomas. Suppression of MMP activity in malignant glioma cells would be meriting to local delivery of genes or chemotherapeutic agents. In this study, we employed a novel MMP inhibitor, SI-27 to investigate inhibition of cell invasiveness in human malignant glioma cell lines, U87MG, U251MG, and U373MG. We evaluated with zymogram, reverse zymogram, and cell invasion assay after exposure of SI-27 for 24 h followed by preliminary MTT assay to find non-cytotoxic dose range, 5, 10, 50, 100 microg/ml compared with non-treatment group as the control. Common to three glioma cell lines, zymogram disclosed that expressions of MMP-2 and -9 were suppressed in a dose-dependent fashion, meanwhile those of tissue inhibitor of MMP (TIMMP) in reverse zymogram were not. The numbers of invading cells through Boyden chamber were significantly reduced in a dose-dependent manner, while those with 5 microg/ml were not diminished common to those three lines. In conclusion, dose concentration ranging 10-100 microg/ml of SI-27 inhibited MMP-2 and -9 mediated cell invasiveness in malignant glioma cell lines. This is the first report for chemotherapeutic effect of SI-27 on glioma cells.
Noha
M
M
Department of Neurosurgery, Nippon Medical School, Tokyo, Japan.
Yoshida
D
D
Watanabe
K
K
Teramoto
A
A
D001932:Brain Neoplasms / Q000473:pathology*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005910:Glioma / Q000473:pathology*; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D009842:Oligopeptides / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology*; D019714:Tissue Inhibitor of Metalloproteinases / Q000032:analysis; D014407:Tumor Cells, Cultured
D061965:Matrix Metalloproteinase Inhibitors; D009842:Oligopeptides; D011480:Protease Inhibitors; C421267:SI 27; D019714:Tissue Inhibitor of Metalloproteinases