The inhibitory effect of matrix metalloproteinase inhibitor ONO-4817 on lymph node metastasis in tongue carcinoma.

Abstract

BACKGROUND:

ONO-4817 is a novel matrix metalloproteinase (MMP) inhibitor which has a broad inhibitory spectrum for MMPs. We investigated the inhibitory effect of ONO-4817 on cervical lymph node metastasis of tongue carcinoma.

MATERIALS AND METHODS:

HSC-3-M3, a cell line derived from human tongue carcinoma with high metastatic potential for lymph node, was used. The direct cytotoxicity of ONO-4817 was assessed by MTT assay and the gelatinolytic activity by gelatin zymography and film in situ zymography (FIZ). The inhibitory effect on lymph node metastasis was examined by orthotopic implantation model with nude mice.

RESULTS:

ONO-4817 had no direct cyototoxicity on HSC-3-M3 cells. Gelatin zymography and FIZ demonstrated a suppression of MMP-9 activation and a marked inhibition of gelatinolysis. Additionally, a suppression of cervical lymph node metastasis was shown by therapeutic experiment.

CONCLUSION:

The MMP inhibitor, ONO-4817, is a candidate for adjunctive therapy of cervical lymph node metastasis in tongue carcinoma.

• Authors: Taku Yamashita, Masato Fujii, Toshiki Tomita, Ryuichiro Ishiguro, Masatsugu Tashiro, Yutaka Tokumaru, Yorihisa Imanishi, Minoru Kanke, Kaoru Ogawa, Kaori Kameyama, Yoshihide Otani
• Journal: Anticancer research (Anticancer Res) 2003 May-Jun Vol. 23 Issue 3B Pg. 2297-302 ISSN: 0250-7005 [Print] Greece
• PMID: 12894506 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Precursors
• Matrix Metalloproteinase Inhibitors
• N-hydroxy-5-ethoxymethyloxy-2-methyl-4-(4-phenoxybenzoyl)aminopentanamide
• Phenyl Ethers
• Collagenases
• pro-matrix metalloproteinase 9
• Matrix Metalloproteinase 9

Topics

• Animals
• Carcinoma, Squamous Cell (drug therapy, enzymology, secondary)
• Cell Division (drug effects)
• Collagenases (metabolism)
• Enzyme Precursors (antagonists & inhibitors, metabolism)
• Humans
• Lymphatic Metastasis
• Male
• Matrix Metalloproteinase 9 (metabolism)
• Matrix Metalloproteinase Inhibitors
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Phenyl Ethers (pharmacology)
• Tongue Neoplasms (drug therapy, enzymology, pathology)
• Tumor Cells, Cultured
• Weight Loss (drug effects)
• Xenograft Model Antitumor Assays