We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Anti-invasive and antiangiogenic effects ofMMI-166 on malignant glioma cells.
- Authors
Nakabayashi, Hiromichi; Yawata, Toshio; Shimizu, Keiji
- Abstract
Background: The constitutive overexpression of matrix metalloproteinases (MMPs) is frequently observed in malignant tumours. In particular, MMP-2 and MMP-9 have been reported to be closely associated with invasion and angiogenesis in malignant gliomas. Our study aimed to evaluate the antitumour effects of MMI-166 (Nalpha-[4-(2- Phenyl-2H- tetrazole-5-yl) phenyl sulfonyl]-D-tryptophan), a third generation MMP inhibitor, on three human glioma cell lines (T98G, U87MG, and ONS12) in vitro and in vivo. Methods: The effects of MMI-166 on the gelatinolytic activity was analysed by gelatine zymography. The anti-invasive effect of MMI-166 was analysed by an in vitro invasion assay. An in vitro angiogenesis assay was also performed. In vitro growth inhibition of glioma cells by MMI-166 was determined by the MTT assay. The effect of MMI-166 on an orthotropic implantation model using athymic mice was also evaluated. Results: Gelatine zymography revealed that MMP-2 and MMP-9 activities were suppressed by MMI-166. The invasion of glioma cells was suppressed by MMI-166. The angiogenesis assay showed that MMI-166 had a suppressive effect on glioma cell-induced angiogenesis. However, MMI-166 did not suppress glioma cell proliferation in the MTT assay. In vivo, MMI-166 suppressed tumour growth in athymic mice implanted orthotropically with T98G cells and showed an inhibitory effect on tumour-induced angiogenesis and tumour growth. This is the first report of the effect of a third generation MMP inhibitor on malignant glioma cells. Conclusions: These results suggest that MMI-166 may have potentially suppressive effects on the invasion and angiogenesis of malignant gliomas.
- Subjects
METALLOPROTEINASES; TUMORS; NEOVASCULARIZATION; GLIOMAS; CELL lines
- Publication
BMC Cancer, 2010, Vol 10, p339
- ISSN
1471-2407
- Publication type
Article
- DOI
10.1186/1471-2407-10-339