title: Evaluation of Suppressive Effects of Tranilast on the Invasion/Metastasis Mechanism in a Murine Pancreatic Cancer Cell Line.
abstract: Numerous studies have investigated the mechanism of the antitumor effect of tranilast, well known as an antiallergic drug. Herein, we investigated the mechanism of the antitumor effects of tranilast using murine PAN 02 cell line.
  
  
  
  In an allograft mouse model, the number of metastatic sites in the liver was counted. Wound healing and chemoinvasion assay were performed to evaluate migration and invasive ability of PAN 02, respectively. Activities of matrix metalloproteinases (MMPs) were evaluated by gelatin zymography. The expression of cofactors in the activation of MMP-2 was assessed by immunohistochemical staining at the front of metastasis.
  
  
  
  The number of metastatic sites was reduced in tranilast-treated groups. Migration ability and tumor invasiveness were significantly inhibited by tranilast in a dose-dependent manner. Gelatin zymography revealed inhibition of MMP-2 activity. Immunohistochemical staining showed remarkable attenuation of tissue inhibitor of metalloproteinase (TIMP-) 2 expression in tranilast-treated groups.
  
  
  
  Tissue inhibitor of metalloproteinase 2 is necessary for MMP-2 activation with interaction between membrane type 1-MMP and proMMP-2. These results suggested that tranilast may inhibit MMP-2 activation through attenuating TIMP-2 expression, resulting in inhibition of tumor invasion and metastasis. Our results showed possibility of tranilast in clinical application for novel cancer therapy.
authors.affiliation: From the *Department of Surgery, Kitasato Institute Hospital; †Department of Surgery, Keio University School of Medicine; ‡Biomedical Laboratory, Kitasato Institute Hospital; and §Department of Pharmacy, Center for Clinical Pharmacy and Clinical Science, Kitasato University, Tokyo, Japan.
authors.forename: Munehisa
authors.initials: M
authors.lastname: Kaneda
authors.forename: Hideaki
authors.initials: H
authors.lastname: Obara
authors.forename: Keiichi
authors.initials: K
authors.lastname: Suzuki
authors.forename: Osamu
authors.initials: O
authors.lastname: Takeuchi
authors.forename: Asako
authors.initials: A
authors.lastname: Takizawa
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Osaku
authors.forename: Hajime
authors.initials: H
authors.lastname: Matsubara
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kitagawa
mesh_terms: D064591:Allografts; D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D008113:Liver Neoplasms / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
chemical_list: D018926:Anti-Allergic Agents; D062367:ortho-Aminobenzoates; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; C012293:tranilast