The potential for a selective cyclooxygenase-2 inhibitor in the prevention of liver metastasis in human colorectal cancer

Takeyoshi Yamauchi, Masahiko Watanabe, Hirotoshi Hasegawa, Hideki Nishibori, Yoshiyuki Ishii, Hideki Tatematsu, Kentaro Yamamoto, Tetsuro Kubota, Masaki Kitajima

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Abstract

In a previous report we noted that cyclooxygenase-2 (COX-2) expression in clinical colorectal cancer is closely related to liver metastasis and survival. The aim of the present study was to clarify the role of COX-2 in liver metastasis and to examine the potential for a selective COX-2 inhibitor as a novel therapeutic agent in the treatment of colorectal cancer. Materials and Methods: COX-2 expression of 6 kinds of human colon cancer cell lines, with various potentials for liver metastasis, were assessed by Western blot and reverse transcriptase polymerase chain reaction (RT-PCR). In human tumor xenografts/severe combined immune - deficient (SCID) mouse, we examined the effects of a selective COX-2 inhibitor (JTE-522) on tumor growth or liver metastasis of HT-29, a highly - metastatic cell line, or on COLO205, a non - metastatic cell line. The effect of JTE-522 on vascular endothelial growth factor (VEGF) expression and the activity of matrix metalloproteinases (MMPs) in HT-29 and COLO205 were assessed by enzyme-linked immunosorbent assay (ELISA) and gelatin zymography, respectively. Results: COX-2 was expressed in all metastatic cell lines but not in the non - metastatic lines. JTE-522 prevented the liver metastasis of HT-29, but not the subcutaneous growth of HT-29 and COLO205 in SCID mice. In vitro, JTE-522 suppressed VEGF expression, but did not affect MMP production in HT-29; an inhibitory effect was not found in COLO205. Conclusion: A selective COX-2 inhibitor of JTE-522, was found to prevent liver metastases of colon cancer by suppressing VEGF expression, and therefore, COX-2 possibly plays an important role in liver metastasis of human colon cancer via the regulation of VEGF expression.

Original languageEnglish
Pages (from-to)245-249
Number of pages5
JournalAnticancer research
Volume23
Issue number1 A
Publication statusPublished - 2003 Jan 1

Keywords

  • Cyclooxygenase-2 (COX-2)
  • Human colorectal cancer cell lines
  • Liver metastasis
  • Selective COX-2 inhibitor

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Yamauchi, T., Watanabe, M., Hasegawa, H., Nishibori, H., Ishii, Y., Tatematsu, H., Yamamoto, K., Kubota, T., & Kitajima, M. (2003). The potential for a selective cyclooxygenase-2 inhibitor in the prevention of liver metastasis in human colorectal cancer. Anticancer research, 23(1 A), 245-249.