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

Taku Yamashita, Masato Fujii, Toshiki Tomita, Ryuichiro Ishiguro, Masatsugu Tashiro, Yutaka Tokumaru, Yorihisa Imanishi, Minoru Kanke, Kaoru Ogawa, Kaori Kameyama, Yoshihide Otani

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2297-2302
Number of pages6
JournalAnticancer research
Volume23
Issue number3 B
Publication statusPublished - 2003 May 1

Keywords

  • Head and neck squamous cell carcinoma
  • Lymph node metastasis
  • Matrix metalloproteinase inhibitor
  • ONO-4817
  • Orthotopic implantation model

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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