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

Gynecol Oncol. 2002 Apr;85(1):103-7. doi: 10.1006/gyno.2001.6573.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / enzymology
  • Adenocarcinoma / genetics
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / enzymology
  • Carcinoma, Squamous Cell / genetics
  • Enzyme Inhibitors / pharmacology*
  • Female
  • Gelatinases / antagonists & inhibitors
  • Gelatinases / metabolism
  • Humans
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / biosynthesis
  • Isoenzymes / genetics
  • Matrix Metalloproteinase 15
  • Matrix Metalloproteinase 16
  • Matrix Metalloproteinase 2 / biosynthesis
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase Inhibitors*
  • Matrix Metalloproteinases / biosynthesis
  • Matrix Metalloproteinases / genetics
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases / antagonists & inhibitors
  • Metalloendopeptidases / biosynthesis
  • Metalloendopeptidases / genetics
  • Neoplasm Invasiveness
  • Sulfonamides / pharmacology*
  • Tissue Inhibitor of Metalloproteinase-1 / biosynthesis
  • Tissue Inhibitor of Metalloproteinase-1 / genetics
  • Tissue Inhibitor of Metalloproteinase-2 / biosynthesis
  • Tissue Inhibitor of Metalloproteinase-2 / genetics
  • Tumor Cells, Cultured
  • Uterine Cervical Neoplasms / drug therapy*
  • Uterine Cervical Neoplasms / enzymology
  • Uterine Cervical Neoplasms / genetics

Substances

  • Enzyme Inhibitors
  • Isoenzymes
  • MMP15 protein, human
  • MMP16 protein, human
  • Matrix Metalloproteinase Inhibitors
  • N-alpha-(4-(2-phenyl-2H- tetrazole-5-yl) phenyl sulfonyl)-D-tryptophan
  • Sulfonamides
  • Tissue Inhibitor of Metalloproteinase-1
  • Tissue Inhibitor of Metalloproteinase-2
  • Gelatinases
  • Matrix Metalloproteinase 15
  • Matrix Metalloproteinase 16
  • Matrix Metalloproteinases
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases
  • Matrix Metalloproteinase 2