title: 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.
  
  
  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.
  
  
  CONCLUSIONS
  The MMP inhibitor, ONO-4817, is a candidate for adjunctive therapy of cervical lymph node metastasis in tongue carcinoma.
authors.affiliation: Department of Otolaryngology, Keio University, School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Yamashita
authors.forename: Masato
authors.initials: M
authors.lastname: Fujii
authors.forename: Toshiki
authors.initials: T
authors.lastname: Tomita
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Ishiguro
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Tashiro
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Tokumaru
authors.forename: Yorihisa
authors.initials: Y
authors.lastname: Imanishi
authors.forename: Minoru
authors.initials: M
authors.lastname: Kanke
authors.forename: Kaoru
authors.initials: K
authors.lastname: Ogawa
authors.forename: Kaori
authors.initials: K
authors.lastname: Kameyama
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Otani
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000201:enzymology / Q000556:secondary; D002455:Cell Division / Q000187:drug effects; D017364:Collagenases / Q000378:metabolism; D004792:Enzyme Precursors / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010647:Phenyl Ethers / Q000494:pharmacology*; D014062:Tongue Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D014407:Tumor Cells, Cultured; D015431:Weight Loss / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D004792:Enzyme Precursors; D061965:Matrix Metalloproteinase Inhibitors; C414368:N-hydroxy-5-ethoxymethyloxy-2-methyl-4-(4-phenoxybenzoyl)aminopentanamide; D010647:Phenyl Ethers; D017364:Collagenases; C120487:pro-matrix metalloproteinase 9; D020780:Matrix Metalloproteinase 9