Logo of brjcancerBJC HomepageBJC Advance online publicationBJC Current IssueSubmitting an article to BJCWeb feeds
Br J Cancer. Dec 1999; 81(8): 1274–1279.
PMCID: PMC2362975

Inhibition of haematogenous metastasis of colon cancer in mice by a selective COX-2 inhibitor, JTE-522

Abstract

It is proposed that non-steroidal anti-inflammatory drugs (NSAIDs) reduce colorectal tumorigenesis by inhibition of cyclooxygenase (COX). COX is a key enzyme in the conversion of arachidonic acid to prostaglandins and two isoforms of COX have been characterized, COX-1 and COX-2. Multiple studies have shown that COX-2 is expressed at high levels in colorectal tumours and play a role in colorectal tumorigenesis. Recently it has been reported that selective inhibition of COX-2 inhibits colon cancer cell growth. In this study we investigated the effect of a selective COX-2 inhibitor (JTE-522) on haematogenous metastasis of colon cancer. For this purpose, we selected a murine colon cancer cell line, colon-26, that constitutively expresses the COX-2 protein. The subclone P expressed a high level of COX-2 and the subclone 5 expressed a low level. The colon-26 subclones were injected into the tail vein of BALB/c mice. JTE-522 was given intraperitoneally every day from the day prior to cancer cell injection, and the mice were sacrificed 16 days after cell injection. Lung metastases were compared between groups with and without JTE-522. In the mice injected with subclone P, the number of lung metastatic nodules was significantly reduced in the treated group. However, in the mice injected with subclone 5, there was little difference between the control and the treated groups. These results indicate that there may be a direct link between inhibition of haematogenous metastasis of colon cancer and selective inhibition of COX-2, and that selective COX-2 inhibitors may be a novel class of therapeutic agents not only for colorectal tumorigenesis but also for haematogenous metastasis of colon cancer. © 1999 Cancer Research Campaign

Keywords: COX-2, colon cancer, metastasis, apoptosis, MMP, selective COX-2 inhibitor

Full Text

The Full Text of this article is available as a PDF (165K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Chambers AF, Matrisian LM. Changing views of the role of matrix metalloproteinases in metastasis. J Natl Cancer Inst. 1997 Sep 3;89(17):1260–1270. [PubMed]
  • DuBois RN, Awad J, Morrow J, Roberts LJ, 2nd, Bishop PR. Regulation of eicosanoid production and mitogenesis in rat intestinal epithelial cells by transforming growth factor-alpha and phorbol ester. J Clin Invest. 1994 Feb;93(2):493–498. [PMC free article] [PubMed]
  • Eberhart CE, Coffey RJ, Radhika A, Giardiello FM, Ferrenbach S, DuBois RN. Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology. 1994 Oct;107(4):1183–1188. [PubMed]
  • Elder DJ, Halton DE, Hague A, Paraskeva C. Induction of apoptotic cell death in human colorectal carcinoma cell lines by a cyclooxygenase-2 (COX-2)-selective nonsteroidal anti-inflammatory drug: independence from COX-2 protein expression. Clin Cancer Res. 1997 Oct;3(10):1679–1683. [PubMed]
  • Folkman J. What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst. 1990 Jan 3;82(1):4–6. [PubMed]
  • Form DM, Auerbach R. PGE2 and angiogenesis. Proc Soc Exp Biol Med. 1983 Feb;172(2):214–218. [PubMed]
  • Fujimoto-Ouchi K, Tamura S, Mori K, Tanaka Y, Ishitsuka H. Establishment and characterization of cachexia-inducing and -non-inducing clones of murine colon 26 carcinoma. Int J Cancer. 1995 May 16;61(4):522–528. [PubMed]
  • Giovannucci E, Rimm EB, Stampfer MJ, Colditz GA, Ascherio A, Willett WC. Aspirin use and the risk for colorectal cancer and adenoma in male health professionals. Ann Intern Med. 1994 Aug 15;121(4):241–246. [PubMed]
  • Giovannucci E, Egan KM, Hunter DJ, Stampfer MJ, Colditz GA, Willett WC, Speizer FE. Aspirin and the risk of colorectal cancer in women. N Engl J Med. 1995 Sep 7;333(10):609–614. [PubMed]
  • Hara A, Yoshimi N, Niwa M, Ino N, Mori H. Apoptosis induced by NS-398, a selective cyclooxygenase-2 inhibitor, in human colorectal cancer cell lines. Jpn J Cancer Res. 1997 Jun;88(6):600–604. [PubMed]
  • Hasegawa M, Arai T, Ihara Y. Immunochemical evidence that fragments of phosphorylated MAP5 (MAP1B) are bound to neurofibrillary tangles in Alzheimer's disease. Neuron. 1990 Jun;4(6):909–918. [PubMed]
  • Horak ER, Leek R, Klenk N, LeJeune S, Smith K, Stuart N, Greenall M, Stepniewska K, Harris AL. Angiogenesis, assessed by platelet/endothelial cell adhesion molecule antibodies, as indicator of node metastases and survival in breast cancer. Lancet. 1992 Nov 7;340(8828):1120–1124. [PubMed]
  • Jones DA, Carlton DP, McIntyre TM, Zimmerman GA, Prescott SM. Molecular cloning of human prostaglandin endoperoxide synthase type II and demonstration of expression in response to cytokines. J Biol Chem. 1993 Apr 25;268(12):9049–9054. [PubMed]
  • Kargman SL, O'Neill GP, Vickers PJ, Evans JF, Mancini JA, Jothy S. Expression of prostaglandin G/H synthase-1 and -2 protein in human colon cancer. Cancer Res. 1995 Jun 15;55(12):2556–2559. [PubMed]
  • Kato N, Nawa A, Tamakoshi K, Kikkawa F, Suganuma N, Okamoto T, Goto S, Tomoda Y, Hamaguchi M, Nakajima M. Suppression of gelatinase production with decreased invasiveness of choriocarcinoma cells by human recombinant interferon beta. Am J Obstet Gynecol. 1995 Feb;172(2 Pt 1):601–606. [PubMed]
  • Kawamori T, Rao CV, Seibert K, Reddy BS. Chemopreventive activity of celecoxib, a specific cyclooxygenase-2 inhibitor, against colon carcinogenesis. Cancer Res. 1998 Feb 1;58(3):409–412. [PubMed]
  • Kujubu DA, Fletcher BS, Varnum BC, Lim RW, Herschman HR. TIS10, a phorbol ester tumor promoter-inducible mRNA from Swiss 3T3 cells, encodes a novel prostaglandin synthase/cyclooxygenase homologue. J Biol Chem. 1991 Jul 15;266(20):12866–12872. [PubMed]
  • Liotta LA, Rao CN, Wewer UM. Biochemical interactions of tumor cells with the basement membrane. Annu Rev Biochem. 1986;55:1037–1057. [PubMed]
  • Mahadevan V, Hart IR. Metastasis and angiogenesis. Acta Oncol. 1990;29(1):97–103. [PubMed]
  • Majima M, Isono M, Ikeda Y, Hayashi I, Hatanaka K, Harada Y, Katsumata O, Yamashina S, Katori M, Yamamoto S. Significant roles of inducible cyclooxygenase (COX)-2 in angiogenesis in rat sponge implants. Jpn J Pharmacol. 1997 Oct;75(2):105–114. [PubMed]
  • Marnett LJ. Aspirin and the potential role of prostaglandins in colon cancer. Cancer Res. 1992 Oct 15;52(20):5575–5589. [PubMed]
  • Marnett LJ. Aspirin and related nonsteroidal anti-inflammatory drugs as chemopreventive agents against colon cancer. Prev Med. 1995 Mar;24(2):103–106. [PubMed]
  • Matsushita M, Masaki M, Yagi Y, Tanaka T, Wakitani K. Pharmacological profile of JTE-522, a novel prostaglandin H synthase-2 inhibitor, in rats. Inflamm Res. 1997 Nov;46(11):461–466. [PubMed]
  • O'Banion MK, Sadowski HB, Winn V, Young DA. A serum- and glucocorticoid-regulated 4-kilobase mRNA encodes a cyclooxygenase-related protein. J Biol Chem. 1991 Dec 5;266(34):23261–23267. [PubMed]
  • Oshima M, Dinchuk JE, Kargman SL, Oshima H, Hancock B, Kwong E, Trzaskos JM, Evans JF, Taketo MM. Suppression of intestinal polyposis in Apc delta716 knockout mice by inhibition of cyclooxygenase 2 (COX-2). Cell. 1996 Nov 29;87(5):803–809. [PubMed]
  • Piazza GA, Rahm AK, Finn TS, Fryer BH, Li H, Stoumen AL, Pamukcu R, Ahnen DJ. Apoptosis primarily accounts for the growth-inhibitory properties of sulindac metabolites and involves a mechanism that is independent of cyclooxygenase inhibition, cell cycle arrest, and p53 induction. Cancer Res. 1997 Jun 15;57(12):2452–2459. [PubMed]
  • Reddy BS, Rao CV, Seibert K. Evaluation of cyclooxygenase-2 inhibitor for potential chemopreventive properties in colon carcinogenesis. Cancer Res. 1996 Oct 15;56(20):4566–4569. [PubMed]
  • Sano H, Kawahito Y, Wilder RL, Hashiramoto A, Mukai S, Asai K, Kimura S, Kato H, Kondo M, Hla T. Expression of cyclooxygenase-1 and -2 in human colorectal cancer. Cancer Res. 1995 Sep 1;55(17):3785–3789. [PubMed]
  • Seed MP, Brown JR, Freemantle CN, Papworth JL, Colville-Nash PR, Willis D, Somerville KW, Asculai S, Willoughby DA. The inhibition of colon-26 adenocarcinoma development and angiogenesis by topical diclofenac in 2.5% hyaluronan. Cancer Res. 1997 May 1;57(9):1625–1629. [PubMed]
  • Sheng H, Shao J, Kirkland SC, Isakson P, Coffey RJ, Morrow J, Beauchamp RD, DuBois RN. Inhibition of human colon cancer cell growth by selective inhibition of cyclooxygenase-2. J Clin Invest. 1997 May 1;99(9):2254–2259. [PMC free article] [PubMed]
  • Thun MJ, Namboodiri MM, Heath CW., Jr Aspirin use and reduced risk of fatal colon cancer. N Engl J Med. 1991 Dec 5;325(23):1593–1596. [PubMed]
  • Thun MJ, Namboodiri MM, Calle EE, Flanders WD, Heath CW., Jr Aspirin use and risk of fatal cancer. Cancer Res. 1993 Mar 15;53(6):1322–1327. [PubMed]
  • Tsujii M, Kawano S, DuBois RN. Cyclooxygenase-2 expression in human colon cancer cells increases metastatic potential. Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3336–3340. [PMC free article] [PubMed]
  • Tsujii M, Kawano S, Tsuji S, Sawaoka H, Hori M, DuBois RN. Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell. 1998 May 29;93(5):705–716. [PubMed]
  • Williams CS, DuBois RN. Prostaglandin endoperoxide synthase: why two isoforms? Am J Physiol. 1996 Mar;270(3 Pt 1):G393–G400. [PubMed]
  • Xie W, Herschman HR. v-src induces prostaglandin synthase 2 gene expression by activation of the c-Jun N-terminal kinase and the c-Jun transcription factor. J Biol Chem. 1995 Nov 17;270(46):27622–27628. [PubMed]
  • Ziche M, Jones J, Gullino PM. Role of prostaglandin E1 and copper in angiogenesis. J Natl Cancer Inst. 1982 Aug;69(2):475–482. [PubMed]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Compound
    Compound
    PubChem Compound links
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...