Anti-invasive and antiangiogenic effects of MMI-166 on malignant glioma cells

BMC Cancer

Research Article

Keiji Shimizu¹  Hiromichi Nakabayashi¹  Toshio Yawata¹ 

[1] Department of Neurosurgery, Kochi Medical School Kochi University, Nankoku, Japan;

关键词: Glioma Cell;    Malignant Glioma;    Glioma Cell Line;    T98G Cell;    Gelatinolytic Activity;   

DOI  :  10.1186/1471-2407-10-339

 received in 2010-02-03, accepted in 2010-06-29,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundThe 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.MethodsThe 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.ResultsGelatine 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.ConclusionsThese results suggest that MMI-166 may have potentially suppressive effects on the invasion and angiogenesis of malignant gliomas.

【 授权许可】

CC BY   
© Nakabayashi et al; licensee BioMed Central Ltd. 2010