What is the role of cyclooxygenase (COX) deficiency in colon carcinoma?

Updated: Feb 19, 2019
  • Author: George T Griffing, MD; Chief Editor: George T Griffing, MD  more...
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COX expression has been implicated in colon carcinoma since epidemiologic studies first described reduced mortality rates in subjects taking aspirin. [23, 24] Initially, Tsujii and DuBois studied the effects of COX-2 overexpression by transfecting rat intestinal epithelium. [25] They demonstrated that overexpression increased adhesion and inhibited apoptosis, perhaps enhancing tumorigenic potential. [13]

In a study in which Oshima and colleagues bred mice with APC mutations similar to those of humans, COX was uncovered as a significant factor in colon carcinoma. [26, 27] The investigators reported that mice carrying an APC mutation and who were wild type for COX-2 expression developed an average of 652 polyps at 10 weeks, whereas heterozygous mice developed 224 polyps, and null mice developed 93 polyps. They also found that drugs that inhibited COX-2 (but not COX-1) greatly reduced polyp formation.

Further research by Langenbach and coauthors, using multiple intestinal neoplasia mice (which led to 100% incidence of carcinoma), showed that COX-1 and COX-2 deficiency decreased polyps by 70-80%. [6] Although a correlation exists between COX expression and colon carcinoma, the mechanism of action remains unknown. [28] Moreover, the described studies may demonstrate only one of many antitumorigenic pathways that, irrespective of COX dependence, are affected by NSAIDs. [29, 30, 31]

Nevertheless, studies have shown that NSAIDs, including selective COX-2 inhibitors (celecoxib), augment the sensitivity of many kinds of tumors toward chemotherapeutics. [32] In that regard, celecoxib and 5-fluorouracil used in combination have a synergistic antitumor effect in a colon cancer mouse model. The mechanism of this interaction may be activation of an apoptosis signal. [33]

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