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 rela tion to the cell invasion of gliomas. Suppression of MMP activity in malign ant glioma cells would be meriting to local delivery of genes or chemothera peutic agents. In this study, we employed a novel MMP inhibitor, SI-27 to i nvestigate inhibition of cell invasiveness in human malignant glioma cell l ines, U87MG, U251MG, and U373MG. We evaluated with zymogram, reverse zymogr am, and cell invasion assay after exposure of SI-27 for 24 h followed by pr eliminary MTT assay to find non-cytotoxic dose range, 5, 10, 50, 100 mug/ml compared with non-treatment group as the control. Common to three glioma c ell lines, zymogram disclosed that expressions of MMP-2 and -9 were suppres sed in a dose-dependent fashion, meanwhile those of tissue inhibitor of MMP (TIMMP) in reverse zymogram were not. The numbers of invading cells throug h Boyden chamber were significantly reduced in a dose-dependent manner, whi le those with 5 mug/ml were not diminished common to those three lines. In conclusion, dose concentration ranging 10-100 mug/ml of SI-27 inhibited MMP -2 and -9 mediated cell invasiveness in malignant glioma cell lines. This i s the first report for chemotherapeutic effect of SI-27 on glioma cells.