COX-2 and colorectal cancer

被引:53
作者
Ferrández, A [1 ]
Prescott, S [1 ]
Burt, RW [1 ]
机构
[1] Univ Utah, Huntsman Canc Inst, Dept Outreach & Prevent, Salt Lake City, UT 84112 USA
关键词
colorectal cancer; cyclooxygenase; prostaglandins; NSAIDs;
D O I
10.2174/1381612033454036
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Metabolites of arachidonic acid participate in normal growth responses and in aberrant cellular growth and proliferation, including carcinogenesis. The key step in the conversion of free arachidonic acid to prostaglandins is catalyzed by the cyclooxygenase enzyme (COX). There are two COX enzymes, COX-1 and COX-2. COX-1 is expressed constitutively and is part of normal cell metabolic functions. COX-2, on the other hand, is induced and expressed in neoplastic growths. The connection between COX expression and carcinogenesis was first implicated in studies that demonstrated the efficacy of aspirin and non-steroidal anti-inflammatory drugs to reduce the relative risk of colon cancer and also promote tumor regression in both humans and animal models of colon cancer. Investigation of the molecular basis of these observations showed that high levels of COX-2 protein were present in both human and animal colorectal tumors. A variety of evidence gathered from epidemiological, whole animal, and cellular studies indicate that unregulated COX-2 expression is a rate-limiting step in tumorigenesis and also that the loss of regulation occurs early in carcinogenesis. The interest in the COX-2 enzyme is that specific inhibition of COX-2 could theoretically avoid the gastrointestinal and other complications observed with the use of nonspecific COX inhibitors (most NSAIDs) or COX-1 inhibitors. The mechanisms by which COX-2 inhibitors lead to decreased colon carcinogenesis are not fully understood but they involve an increase not only in COX-2 dependent but also in COX-2 independent mechanisms.
引用
收藏
页码:2229 / 2251
页数:23
相关论文
共 242 条
  • [101] Why is Hu where? Shuttling of early-response-gene messenger RNA subsets
    Keene, JD
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (01) : 5 - 7
  • [102] Rectal epithelial apoptosis in familial adenomatous polyposis patients treated with sulindac
    Keller, JJ
    Offerhaus, GJA
    Polak, M
    Goodman, SN
    Zahurak, ML
    Hylind, LM
    Hamilton, SR
    Giardiello, FM
    [J]. GUT, 1999, 45 (06) : 822 - 828
  • [103] Effects of cyclooxygenase-2 inhibitor NS-398 on APC and c-myc expression in rat colon carcinogenesis induced by azoxymethane
    Kishimoto, Y
    Yashima, K
    Morisawa, T
    Shiota, G
    Kawasaki, H
    Hasegawa, J
    [J]. JOURNAL OF GASTROENTEROLOGY, 2002, 37 (03) : 186 - 193
  • [104] Lipopolysaccharide increases cyclo-oxygenase-2 expression in a colon carcinoma cell line through nuclear factor-κB activation
    Kojima, M
    Morisaki, T
    Izuhara, K
    Uchiyama, A
    Matsunari, Y
    Katano, M
    Tanaka, M
    [J]. ONCOGENE, 2000, 19 (09) : 1225 - 1231
  • [105] KUDO T, 1980, GANN, V71, P260
  • [106] Colorectal cancer risk, chronic illnesses, operations and medications: case-control results from the Melbourne Colorectal Cancer Study (Reprinted from Cancer Research, vol 48, pg 4399-404, 1988)
    Kune, Gabriel A.
    Kune, Susan
    Watson, Lyndsey F.
    [J]. INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, 2007, 36 (05) : 951 - 957
  • [107] Prostaglandin H synthase 2 is expressed abnormally in human colon cancer: Evidence for a transcriptional effect
    Kutchera, W
    Jones, DA
    Matsunami, N
    Groden, J
    McIntyre, TM
    Zimmerman, GA
    White, RL
    Prescott, SM
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (10) : 4816 - 4820
  • [108] SULINDAC CAUSES REGRESSION OF RECTAL POLYPS IN FAMILIAL ADENOMATOUS POLYPOSIS
    LABAYLE, D
    FISCHER, D
    VIELH, P
    DROUHIN, F
    PARIENTE, A
    BORIES, C
    DUHAMEL, O
    TROUSSET, M
    ATTALI, P
    [J]. GASTROENTEROLOGY, 1991, 101 (03) : 635 - 639
  • [109] Interactions of CCCH zinc finger proteins with mRNA - Binding of tristetraprolin-related zinc finger proteins to Au-rich elements and destabilization of mRNA
    Lai, WS
    Carballo, E
    Thorn, JM
    Kennington, EA
    Blackshear, PJ
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (23) : 17827 - 17837
  • [110] Effect of anti-inflammatory drugs on overall risk of common cancer: case-control study in general practice research database
    Langman, MJS
    Cheng, KK
    Gilman, EA
    Lancashire, RJ
    [J]. BRITISH MEDICAL JOURNAL, 2000, 320 (7250) : 1642 - 1646