Anti-invasive effect of MMI-166, a new selective matrix metalloproteinase inhibitor, in cervical carcinoma cell lines

Objectives. The aim of our study was to evaluate the anti-invasive effect of MMI-166, a new matrix metalloproteinase (MMP) inhibitor in cervical carcinoma cell lines. Methods. We analyzed the invasive activities of cervical carcinoma cell lines (CAC-1, CaSki, and SiHa) and the gene expression of various matrix proteinases (matrix metalloproteinase-1 [MMP-1], MMP-2, MMP-9, membrane-type MMP type 1 [MT1-MMP], MT2-MMP, and MT3-MMP) and their inhibitors (tissue inhibitor of metalloproteinase type 1 [TIMP-1] and TIMP-2). The effect of MMI-166 was analyzed by in vitro invasion assay. The cytotoxicity of MMI-166 was determined by MTT assay. The gelatinase activity was analyzed by gelatin zymography. Results. Cervical carcinoma cell lines, which produced both MMP-2 and MT1-MMP, showed invasive capacity in the in vitro invasion assay. The invasion of cervical carcinoma cells was suppressed by MMI-166. No remarkable suppression of the proliferation by MMI-166 was observed in the MTT assay. Gelatin zymography revealed complete suppression of MMP-2 activity by MMI-166. Conclusions. MMI-166 inhibited the MMP-2 activity in cervical carcinoma cells and it is useful for the regulation of cervical carcinoma cell invasion. (C) 2002 Elsevier Science (USA).