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

Fingerprint

Cyclooxygenase 2 Inhibitors
Colorectal Neoplasms
Cyclooxygenase 2
Neoplasm Metastasis
Liver
Vascular Endothelial Growth Factor A
Colonic Neoplasms
Cell Line
Matrix Metalloproteinases
Gelatin
Growth
Reverse Transcriptase Polymerase Chain Reaction
Heterografts
Neoplasms
Western Blotting
Enzyme-Linked Immunosorbent Assay
4-(4-cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamide
Survival
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Yamauchi, T., Watanabe, M., Hasegawa, H., Nishibori, H., Ishii, Y., Tatematsu, H., ... 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.

The potential for a selective cyclooxygenase-2 inhibitor in the prevention of liver metastasis in human colorectal cancer. / Yamauchi, Takeyoshi; Watanabe, Masahiko; Hasegawa, Hirotoshi; Nishibori, Hideki; Ishii, Yoshiyuki; Tatematsu, Hideki; Yamamoto, Kentaro; Kubota, Tetsuro; Kitajima, Masaki.

In: Anticancer Research, Vol. 23, No. 1 A, 01.2003, p. 245-249.

Research output: Contribution to journalArticle

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, vol. 23, no. 1 A, pp. 245-249.
Yamauchi T, Watanabe M, Hasegawa H, Nishibori H, Ishii Y, Tatematsu H et al. The potential for a selective cyclooxygenase-2 inhibitor in the prevention of liver metastasis in human colorectal cancer. Anticancer Research. 2003 Jan;23(1 A):245-249.
Yamauchi, Takeyoshi ; Watanabe, Masahiko ; Hasegawa, Hirotoshi ; Nishibori, Hideki ; Ishii, Yoshiyuki ; Tatematsu, Hideki ; Yamamoto, Kentaro ; Kubota, Tetsuro ; Kitajima, Masaki. / The potential for a selective cyclooxygenase-2 inhibitor in the prevention of liver metastasis in human colorectal cancer. In: Anticancer Research. 2003 ; Vol. 23, No. 1 A. pp. 245-249.
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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.",
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