Evaluation of Suppressive Effects of Tranilast on the Invasion/Metastasis Mechanism in a Murine Pancreatic Cancer Cell Line

Munehisa Kaneda, Hideaki Obara, Keiichi Suzuki, Osamu Takeuchi, Asako Takizawa, Masayoshi Osaku, Hajime Matsubara, Yuukou Kitagawa

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Objectives 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. Methods 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. Results 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. Conclusions 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.

Original languageEnglish
Pages (from-to)567-574
Number of pages8
JournalPancreas
Volume46
Issue number4
DOIs
Publication statusPublished - 2017 Apr 1

Fingerprint

Pancreatic Neoplasms
Matrix Metalloproteinase 2
Neoplasm Metastasis
Cell Line
Tissue Inhibitor of Metalloproteinase-2
Gelatin
Staining and Labeling
Matrix Metalloproteinase 14
Anti-Allergic Agents
Neoplasms
tranilast
Matrix Metalloproteinases
Wound Healing
Allografts
Liver

Keywords

  • antitumor effects
  • liver metastasis
  • matrix metalloproteinases 2
  • pancreatic cancer
  • tranilast

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

Cite this

Evaluation of Suppressive Effects of Tranilast on the Invasion/Metastasis Mechanism in a Murine Pancreatic Cancer Cell Line. / Kaneda, Munehisa; Obara, Hideaki; Suzuki, Keiichi; Takeuchi, Osamu; Takizawa, Asako; Osaku, Masayoshi; Matsubara, Hajime; Kitagawa, Yuukou.

In: Pancreas, Vol. 46, No. 4, 01.04.2017, p. 567-574.

Research output: Contribution to journalArticle

Kaneda, Munehisa ; Obara, Hideaki ; Suzuki, Keiichi ; Takeuchi, Osamu ; Takizawa, Asako ; Osaku, Masayoshi ; Matsubara, Hajime ; Kitagawa, Yuukou. / Evaluation of Suppressive Effects of Tranilast on the Invasion/Metastasis Mechanism in a Murine Pancreatic Cancer Cell Line. In: Pancreas. 2017 ; Vol. 46, No. 4. pp. 567-574.
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abstract = "Objectives 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. Methods 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. Results 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. Conclusions 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.",
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