Skip to main content
NCBI home page
Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1997 Dec;88(12):1117–1120. doi: 10.1111/j.1349-7006.1997.tb00337.x

Suppression of Intestinal Polyp Development by Nimesulide, a Selective Cyclooxygenase‐2 Inhibitor, in Min Mice

Seiichi Nakatsugi 1,2, Masato Fukutake 1, Mami Takahashi 1, Kazunori Fukuda 1, Takashi Isoi 2, Yasuaki Taniguchi 3, Takashi Sugimura 1, Keiji Wakabayashi 1,✉
PMCID: PMC5921349  PMID: 9473726

Abstract

Nonsteroidal anti‐inflammatory drugs (NSAIDs) suppress colon carcinogenesis in man and experimental animals. However, conventional NSAIDs inhibit both cyclooxygenase (COX) isoforms, COX‐1 and COX‐2, and cause gastrointestinal side‐effects. Nimesulide, a selective inhibitor of COX‐2, is much less ulcerogenic. We, therefore, examined its influence on the development of intestinal polyps in Min mice. Female Min mice at 4 weeks old were given 400 ppm nimesulide in their diet for 11 weeks. This treatment resulted in a significant reduction of the numbers of both small and large intestinal polyps, the total being 52% of that in untreated control Min mice. The size of the polyps in the nimesulide‐treated group was also significantly decreased. The results suggest that nimesulide is a good candidate as a chemopreventive agent for human colon cancer with low toxicity.

Keywords: Nimesulide, COX‐2 inhibitor, Min mouse, Intestinal polyp

Full Text

The Full Text of this article is available as a PDF (472.8 KB).

REFERENCES

  • 1. ) Thun , M. J‐ , Namboodiri , M. M. and Heath , C. W. , Jr.Aspirin use and reduced risk of fatal colon cancer . N. Engl. J. Med. , 325 , 1593 – 1596 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 2. ) Rao , C. V. , Rivenson , A. , Simi , B. , Zang , E. , Kelloff , G. , Steele , V. and Reddy , B. S.Chemoprevention of colon carcinogenesis by sulindac, a nonsteroidal anti‐inflammatory agent . Cancer Res. , 55 , 1464 – 1472 ( 1995. ). [PubMed] [Google Scholar]
  • 3. ) Reddy , B. S. , Tokumo , K. , Kulkarni , N. , Aligia , C. and Kelloff , G.Inhibition of colon carcinogenesis by prostaglandin synthesis inhibitors and related compounds . Cardnogenesis , 13 , 1019 – 1023 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 4. ) Kinzler , K. W. , Nilbert , M. C. , Su , L. K. , Vogelstein , B. , Bryan , T. M. , Levy , D. B. , Smith , K. J. , Preisinger , A. C. , Hedge , P. , McKechnie , D. , Finniear , R. , Markham , A. , Groffen , J. , Boguski , M. S. , Altschul , S. F. , Horii , A. , Ando , H. , Miyoshi , Y. , Miki , Y. , Nishisho , I. and Nakamura , Y.Identification of FAP locus genes from chromosome 5q21 . Science , 253 , 661 – 665 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 5. ) Nishisho , I. , Nakamura , Y. , Miyoshi , Y. , Miki , Y. , Ando , H. , Horii , A. , Koyama , K. , Utsunomiya , J. , Baba , S. and Hedge , P.Mutations of chromosome 5q21 genes in FAP and eolorectal cancer patients . Science , 253 , 665 – 669 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 6. ) Giardiello , F. M. , Hamilton , S. R. , Krush , A. J. , Piantadosi , S. , Hylind , L. M. , Celano , P. , Booker , S. V. , Robinson , C. R. and Offerhaus , G. J.Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis . N Engl. J. Med. , 328 , 1313 – 1316 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 7. ) Hirata , K. , Itoh , H. and Ohsato , K.Regression of rectal polyps by indomettiacin suppository in familial adenomatous polyposis. Report of two cases . Dis. Colon Rectum , 37 , 943 – 946 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 8. ) Su , L. K. , Kinzler , K. W. , Vogelstein , B. , Preisinger , A. C. , Moser , A. R. , Luongo , C. , Gould , K. A. and Dove , W. F.Multiple intestinal neoplasia caused by a mutation in the murine homolog of the APC gene . Science , 256 , 668 – 670 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 9. ) Shoemaker , A. R. , Gould , K. A. , Luongo , C. , Moser , A. R. and Dove , W. F.Studies of neoplasia in the Min mouse . Biochim. Biophys. Acta , 1332 , F25 – F48 ( 1997. ). [DOI] [PubMed] [Google Scholar]
  • 10. ) Beazer‐Barclay , Y. , Levy , D. B. , Moser , A. R. , Dove , W. F. , Hamilton , S. R. , Vogelstein , B. and Kinzler , K. W.Sulindac suppresses tumorigenesis in the Min mouse . Cardnogenesis , 17 , 1757 – 1760 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 11. ) Boolbol , S. K. , Dannenberg , A. J. , Chadburn , A. , Martucci , C. , Guo , X. J. , Ramonetti , J. T. , Abreu‐Goris , M. , Newmark , H. L. , Lipkin , M. L. , DeCosse , J. J. and BertagnolH , M. M.Cyclooxygenase‐2 overexpression and tumor formation are blocked by sulindac in a murine model of familial adenomatous polyposis . Cancer Res. , 56 , 2556 – 2560 ( 1996. ). [PubMed] [Google Scholar]
  • 12. ) Jacoby , R. F. , Marshall , D. J. , Newton , M. A. , Novakovic , K. , Tutsch , K. , Cole , C. E. , Lubet , R. A. , Kelloff , G. J. , Verma , A. , Moser , A. R. and Dove , W. F.Chemoprevention of spontaneous intestinal adenomas in the 4pcMin mouse model by the nonsteroidal anti‐inflammatory drug piroxicam . Cancer Res. , 56 , 710 – 714 ( 1996. ). [PubMed] [Google Scholar]
  • 13. ) Herschman , H. R.Prostaglandin synthase 2 . Biochim. Biophys. Acta , 1299 , 125 – 140 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 14. ) Eberhart , C. E. , Coffey , R. J. , Radhika , A. , Giardiello , F. M. , Ferrenbach , S. and Dubois , R. N.Up‐regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas . Gastroenterology , 107 , 1183 – 1188 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 15. ) Sano , H. , Kawahito , Y. , Wilder , R. L. , Hashiramoto , A. , Mukai , S. , Asai , K. , Kimura , S. , Kato , H. , Kondo , M. and Hla , T.Expression of cyclooxygenase‐1 and ‐2 in human colorectal cancer . Cancer Res. , 55 , 3785 – 3789 ( 1995. ). [PubMed] [Google Scholar]
  • 16. ) DuBois , R. N. , Radhika , A. , Reddy , B. S. and Entingh , A. J.Increased cyclooxygenase‐2 levels in carcinogen‐induced rat colonic tumors . Gastroenterology , 110 , 1259 – 1262 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 17. ) Williams , C. S. , Luongo , C. , Radhika , A. , Zhang , T. , Lamps , L. W. , Nanney , L. B. , Beauchamp , R. D. and DuBois , R. N.Elevated cyclooxygenase‐2 levels in Min mouse adenomas . Gastroenterology , 111 , 1134 – 1140 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 18. ) Oshima , M. , Dinchuk , J. E. , Kargman , S. L. , Oshima , H. , Hancock , B. , Kwong , E. , Trzaskos , J. M. , Evans , J. F. and Taketo , M. M.Suppression of intestinal polyposis in ApeΔ716 knockout mice by inhibition of cyclooxygenase 2 (COX‐2) . Cell , 87 , 803 – 809 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 19. ) Tsujii , .M. and DuBois , R. N.Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2 . Cell , 83 , 493 – 501 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 20. ) Meade , E. A. , Smith , W. L. and DeWitt , D. L.Differential inhibition of prostaglandin endoperoxide synthase (cyclooxygenase) isozymes by aspirin and other nonsteroidal anti‐inflammatory drugs . J. Biol Chem. , 268 , 6610 – 6614 ( 1993. ). [PubMed] [Google Scholar]
  • 21. ) Weissenbach , R.Clinical trial with nimesulide, a new non‐steroid anti‐inflammatory agent, in rheumatic pathology . J. Int. Med. Res. 9 , 349 – 352 ( 1981. ). [DOI] [PubMed] [Google Scholar]
  • 22. ) Nakatsugi , S. , Terada , N. , Yoshimura , T. , Horie , Y. and Furukawa , M.Effects of nimesulide, a preferential cyclooxygenase‐2 inhibitor, on carrageenan‐induced pleurisy and stress induced gastric lesions in rats . Prostaglandins Leukot. Essent. Fatty Adds , 55 , 395 – 402 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 23. ) Taniguchi , Y. , Ikesue , A. , Yokoyama , K. , Noda , K. , Debuchi , H. , Nakamura , T. , Toda , A. and Shimeno , H.Selective inhibition by nimesulide, a novel non‐steroidal anti‐inflammatory drug, with prostaglandin endoperoxide synthase‐2 activity in‐vitro . Pharm. Sci. , 1 , 173 – 175 ( 1995. ). [Google Scholar]
  • 24. ) Takahashi , M. , Fukutake , M. , Yokota , S. , Ishida , K. , Wakabayashi , K. and Sugimura , T.Suppression of azoxy‐methane‐induced aberrant crypt foci in rat colon by nimesulide, a selective inhibitor of cyclooxygenase‐2 . J. Cancer Res. Clin. Oncol , 166 , 219 – 222 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 25. ) Cipollini , F. , Mecozzi , V. and Altilia , F.Endoscopic assessment of the effects of nimesulide on the gastric mucosa: comparison with indomethacin . Curr. Ther. Res. , 45 , 1042 – 1048 ( 1989. ). [Google Scholar]

Articles from Japanese Journal of Cancer Research : Gann are provided here courtesy of Wiley

RESOURCES