%0 Journal Article
%T Anti-invasive and antiangiogenic effects of MMI-166 on malignant glioma cells
%A Hiromichi Nakabayashi
%A Toshio Yawata
%A Keiji Shimizu
%J BMC Cancer
%D 2010
%I BioMed Central
%R 10.1186/1471-2407-10-339
%X 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.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.These results suggest that MMI-166 may have potentially suppressive effects on the invasion and angiogenesis of malignant gliomas.Malignant gliomas are characterized by high invasive potential and strong angiogenic ability. The control of tumour invasion and angiogenesis are the key problems for the improvement of treatment results of malignant gliomas. Tumour invasion and angiogenic processes are involved in the degradation of the extracellular matrix (ECM) that surrounds tumour cells. Matrix metalloproteinases (MMPs) that degrade various ECM components are frequently expressed in malignant tumours, including gliomas, at higher levels than their benign counterparts [1,2]. MMPs are theoretically promising targets for new drugs to treat cancers. Several MMP inhibitors have been developed, and their clinical trials have begun in cancer patients [3-5]. Nevertheless, many clinical failures have made drug developers prudent, and the era of synthetic MMP inhibitors was though
%U http://www.biomedcentral.com/1471-2407/10/339