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Table of Contents
Vol. 69, Suppl. 1, 2005
Issue release date: September 2005
Oncology 2005;69:28–32
(DOI:10.1159/000086629)

Mechanisms for the Prevention of Gastrointestinal Cancer: The Role of Prostaglandin E2

Backlund M.G. · Mann J.R. · DuBois R.N.
Departments of aMedicine, bCell and Developmental Biology, and cCancer Biology, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Nashville, Tenn., USA

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Abstract

Carcinoma of the colon or rectum represents one of the most common malignancies worldwide with a higher prevalence in industrialized regions. Epidemiologic studies of individuals taking non-steroidal anti-inflammatory drugs (NSAIDs) have shown a significant reduction in colorectal cancer (CRC) mortality compared to those individuals not receiving these agents. NSAIDs inhibit the enzymatic activity of both isoforms of cyclooxygenase (COX-1 and COX-2), while COX-2-selective inhibitors have shown some efficacy in reducing polyp formation. COX-2-derived bioactive lipids, including the primary prostaglandin (PG) generated in colorectal tumors, PGE2, are known to stimulate cell migration, proliferation and tumor-associated neovascularization while inhibiting cell death. Here we briefly review the role of NSAIDs in preventing CRC, as well as the proposed mechanism by which a COX-2-derived PG, PGE2, promotes colon cancer.



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References

  1. Greenlee RT, Murray T, Bolden S, Wingo PA: Cancer statistics, 2000. CA Cancer J Clin 2000;50:7–33.
  2. Vane JR: Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nature 1971;231:232–235.
  3. DuBois RN, Giardiello FM, Smalley WE: Nonsteroidal anti-inflammatory drugs, eicosanoids and colorectal cancer prevention. Gastroenterol Clin North Am 1996;25:773–791.
  4. Pollard M, Luckert PH: Prevention and treatment of primary intestinal tumors in rats by piroxicam. Cancer Res 1989;49:6471–6473.
  5. Sandler RS, Halabi S, Baron JA, Budinger S, Paskett E, Keresztes R, et al: A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer. N Engl J Med 2003;348:883–890.
  6. Baron JA, Cole BF, Sandler RS, Haile RW, Ahnen D, Bresalier R, et al: A randomized trial of aspirin to prevent colorectal adenomas. N Engl J Med 2003;348:891–899.
  7. Wolfe MM, Lichtenstein DR, Singh G: Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs. N Engl J Med 1999;340:1888–1899.
  8. Laine L, Harper S, Simon T, Bath R, Johanson J, Schwartz H, et al: A randomized trial comparing the effect of rofecoxib, a cyclooxygenase 2-specific inhibitor, with that of ibuprofen on the gastroduodenal mucosa of patients with osteoarthritis. Gastroenterology 1999;117:776–783.
  9. Bombardier C, Laine L, Reicin A, Shapiro D, Burgos-Vargas R, Davis B, et al: Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N Engl J Med 2000;343:1520–1528.
  10. Steinbach G, Lynch PM, Phillips RK, Wallace MH, Hawk E, Gordon GB, et al: The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med 2000;342:1946–1952.
  11. Hernandez MR, Tonda R, Pino M, Serradell M, Arderiu G, Escolar G: Evaluation of effects of rofecoxib on platelet function in an in vitro model of thrombosis with circulating human blood. Eur J Clin Invest 2004;34:297–302.
  12. Brinker A, Goldkind L, Bonnel R, Beitz J: Spontaneous reports of hypertension leading to hospitalisation in association with rofecoxib, celecoxib, nabumetone and oxaprozin. Drugs Aging 2004;21:479–484.
  13. Smith WL, DeWitt DL, Garavito RM: Cyclooxygenases: structural, cellular, and molecular biology. Annu Rev Biochem 2000;69:145–182.
  14. DuBois RN, Abramson SB, Crofford L,Gupta RA, Simon LS, Van De Putte LB: Cyclooxygenase in biology and disease. FASEB J 1998;12:1063–1073.
  15. Tai HH, Ensor CM, Tong M, Zhou H, Yan F: Prostaglandin catabolizing enzymes. Prostaglandins Other Lipid Mediat 2002;68–69:483–493.
  16. Rigas B, Goldman IS, Levine L: Altered eicosanoid levels in human colon cancer. J Lab Clin Med 1993;122:518–523.
  17. 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;107:1183–1188.
  18. Oshima M, Dinchuk JE, Kargman SL, Oshima H, Hancock B, Kwong E, et al: Suppression of intestinal polyposis in Apc delta716 knockout mice by inhibition of cyclooxygenase 2 (COX-2). Cell 1996;87:803–809.
  19. Liu HL, Chang SH, Narko K, Trifan OC, Wu MT, Smith E, et al: Over-expression of cyclooxygenase-2 is sufficient to induce tumorigenesis in transgenic mice. J Biol Chem 2001;276:18563–18569.
  20. Neufang G, Furstenberger G, Heidt M, Marks F, Muller-Decker K: Abnormal differentiation of epidermis in transgenic mice constitutively expressing cyclooxygenase-2 in skin. Proc Natl Acad Sci USA 2001;98:7629–7634.
  21. Quidville V, Segond N, Pidoux E, Cohen R, Jullienne A, Lausson S: Tumor growth inhibition by indomethacin in a mouse model of human medullary thyroid cancer: implication of cyclooxygenases and 15-hydroxyprostaglandin dehydrogenase. Endocrinology 2004;145:2561–2571.
  22. Gee JR, Montoya RG, Khaled HM, Sabichi AL, Grossman HB: Cytokeratin 20, AN43, PGDH, and COX-2 expression in transitional and squamous cell carcinoma of the bladder. Urol Oncol 2003;21:266–270.
  23. Backlund MG, Mann JR, Holla VR, Buchanan FG, Tai HH, Musiek ES, Milne GL, Katkuri S, DuBois RN: 15-Hydroxyprostaglandin dehydrogenase is downregulated in colorectal cancer. J Biol Chem 2004;280:3217–3223.
  24. Turini ME, DuBois RN: Cyclooxygenase-2: a therapeutic target. Annu Rev Med 2002;53:35–57.
  25. Watanabe K, Kawamori T, Nakatsugi S, Ohta T, Ohuchida S, Yamamoto H, et al: Role of the prostaglandin E receptor subtype EP1 in colon carcinogenesis. Cancer Res 1999;59:5093–5096.
  26. Mutoh M, Watanabe K, Kitamura T, Shoji Y, Takahashi M, Kawamori T, et al: Involvement of prostaglandin E receptor subtype EP(4) in colon carcinogenesis. Cancer Res 2002;62:28–32.
  27. Sonoshita M, Takaku K, Sasaki N, Sugimoto Y, Ushikubi F, Narumiya S, et al: Acceleration of intestinal polyposis through prostaglandin receptor EP2 in Apc(Delta 716) knockout mice. Nat Med 2001;7:1048–1051.
  28. Hansen-Petrik MB, McEntee MF, Jull B, Shi H, Zemel MB, Whelan J: Prostaglandin E2 protects intestinal tumors from nonsteroidal anti-inflammatory drug-induced regression in Apc(Min/+) mice. Cancer Res 2002;62:403–408.
  29. Kawamori T, Uchiya N, Sugimura T, Wakabayashi K: Enhancement of colon carcinogenesis by prostaglandin E2 administration. Carcinogenesis 2003;24:985–990.
  30. Wang D, Wang H, Shi Q, Katkuri S, Walhi W, Desvergne B, et al: Prostaglandin E2 promotes colorectal adenoma growth via transactivation of the nuclear peroxisome proliferator-activated receptor delta. Cancer Cell 2004;6:285–295.


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