Cyclooxygenase-2 (cox-2) and the inflammogenesis of cancer

Subcell Biochem. 2007:42:93-126. doi: 10.1007/1-4020-5688-5_4.


Cohesive scientific evidence from molecular, animal, and human investigations supports the hypothesis that aberrant induction of COX-2 and up-regulation of the prostaglandin cascade play a significant role in carcinogenesis, and reciprocally, blockade of the process has strong potential for cancer prevention and therapy. Supporting evidence includes the following: [1] expression of constitutive COX-2-catalyzed prostaglandin biosynthesis is induced by most cancer-causing agents including tobacco smoke and its components (polycylic aromatic amines, heterocyclic amines, nitrosamines), essential polyunsaturated fatty acids (unconjugated linoleic acid), mitogens, growth factors, proinflammatory cytokines, microbial agents, tumor promoters, and other epigenetic factors, [2] COX-2 expression is a characteristic feature of all premalignant neoplasms, [3] COX-2 expression is a characteristic feature of all malignant neoplasms, and expression intensifies with stage at detection and cancer progression and metastasis, [4] all essential features of carcinogenesis (mutagenesis, mitogenesis, angiogenesis, reduced apoptosis, metastasis, and immunosuppression) are linked to COX-2-driven prostaglandin (PGE-2) biosynthesis, [5] animal studies show that COX-2 up-regulation (in the absence of genetic mutations) is sufficient to stimulate the transformation of normal cells to invasive cancer and metastatic disease, [6] non-selective COX-2 inhibitors, such as aspirin and ibuprofen, reduce the risk of human cancer and precancerous lesions, and [7] selective COX-2 inhibitors, such as celecoxib, reduce the risk of human cancer and precancerous lesions at all anatomic sites thus far investigated. Results confirming that COX-2 blockade is effective for both cancer prevention and therapy have been tempered by observations that some COX2 inhibitors pose a risk to the cardiovascular system, and more studies are needed in order to determine if certain of these drugs can be taken at dosages that prevent cancer without increasing cardiovascular risk. It is emphasized that the "inflammogenesis model of cancer" is not mutually exclusive and may in fact be synergistic with the accumulation of somatic mutations in tumor suppressor genes and oncogenes or epigenetic factors in the development of cancer.

Publication types

  • Review

MeSH terms

  • Animals
  • Carcinogens / toxicity
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / enzymology
  • Cardiovascular Diseases / genetics
  • Cyclooxygenase 2 / biosynthesis*
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 Inhibitors / therapeutic use
  • Epigenesis, Genetic / drug effects
  • Gene Expression Regulation, Enzymologic* / drug effects
  • Gene Expression Regulation, Neoplastic* / drug effects
  • Humans
  • Inflammation / chemically induced
  • Inflammation / enzymology
  • Inflammation / genetics
  • Inflammation / prevention & control
  • Inflammation Mediators / metabolism
  • Membrane Proteins / biosynthesis*
  • Membrane Proteins / genetics
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Neoplasms / enzymology*
  • Neoplasms / genetics
  • Neoplasms / prevention & control
  • Up-Regulation / drug effects


  • Carcinogens
  • Cyclooxygenase 2 Inhibitors
  • Inflammation Mediators
  • Membrane Proteins
  • Neoplasm Proteins
  • Cyclooxygenase 2
  • PTGS2 protein, human