Cancer Cell Biology

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Inhibitory effect of a selective cyclooxygenase-2 inhibitor on liver metastasis of colon cancer

  1. Isao Nagatsuka1,
  2. Nobuya Yamada1,†,*,
  3. Sadatoshi Shimizu1,
  4. Masaichi Ohira1,
  5. Hiroji Nishino1,
  6. Shuichi Seki2,
  7. Kosei Hirakawa1

Article first published online: 19 JUN 2002

DOI: 10.1002/ijc.10508

Issue

International Journal of Cancer

International Journal of Cancer

Volume 100, Issue 5, pages 515–519, 10 August 2002

Additional Information

How to Cite

Nagatsuka, I., Yamada, N., Shimizu, S., Ohira, M., Nishino, H., Seki, S. and Hirakawa, K. (2002), Inhibitory effect of a selective cyclooxygenase-2 inhibitor on liver metastasis of colon cancer. Int. J. Cancer, 100: 515–519. doi: 10.1002/ijc.10508

Author Information

  1. 1

    Department of Surgical Oncology, Osaka City University Graduate School of Medicine,Osaka, Japan

  2. 2

    Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan

  1. †

    Fax: +81-6-6646-6450

*Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan

  1. †

    Fax: +81-6-6646-6450

Publication History

  1. Issue published online: 17 JUL 2002
  2. Article first published online: 19 JUN 2002
  3. Manuscript Accepted: 26 APR 2002
  4. Manuscript Revised: 22 APR 2002
  5. Manuscript Received: 11 OCT 2001

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Keywords:

  • cyclooxygenase-2;
  • cyclooxygenase-2 inhibitor;
  • colon cancer;
  • liver metastasis;
  • matrix metalloproteinase

Abstract

COX-2 overexpression is recognized in various cancers, but the role of COX-2 in the progression of cancer, including the liver metastasis of colon cancer, is not clearly understood. We examined the role of COX-2 in the mechanism of liver metastasis of colon cancer, using a highly metastasizable colon carcinoma cell line, LM-H3. A COX-2 inhibitor, JTE-522, inhibited cell proliferation and invasion of LM-H3 in vitro and clearly reduced the number of metastatic nodules on the surface of nude mouse livers in vivo. We also examined the effects of JTE-522 on the production of growth factors and MMPs through the use of ELISA and gelatin zymography, respectively. JTE-522 downregulated PDGF production by LM-H3 but had no influence on VEGF production. JTE-522 also inhibited MMP-2 secretion by LM-H3. JTE-522 downregulated PGE2 production, but the associated changes in PGE2 did not affect PDGF and VEGF production by LM-H3. We conclude that JTE-522 downregulated the cell proliferation and invasive potential of LM-H3 by reducing the production of PDGF and MMP-2 and hypothesize that these inhibitory effects on the production of PDGF and MMP-2 can lead to inhibition of liver metastasis of colon cancer. These data indicate that the COX-2 inhibitor JTE-522 has a high potential for use as a clinical agent for the treatment of liver metastasis of colon cancer. © 2002 Wiley-Liss, Inc.

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