Colonic 15-PGDH levels are stable across distance and time and are not perturbed by aspirin intervention

Dig Dis Sci. 2013 Sep;58(9):2615-22. doi: 10.1007/s10620-013-2670-5. Epub 2013 Apr 27.


Background and aims: 15-Hydroxprostaglandin dehydrogenase (15-PGDH) mediates a colon neoplasia suppressor pathway, acting through metabolic antagonism of cyclooxygenase-mediated colon carcinogenesis. To determine whether the colon tumor prevention activity of 15-PGDH acts as a constant or variable effect among individuals, we determined whether 15-PGDH levels remain stable over subsite and time in the human colon, determined the extent of differences in 15-PGDH levels between different individuals, and determined whether 15-PGDH modulation mediates any part of the anti-colon tumor effect of aspirin.

Methods: Using real-time PCR, we measured 15-PGDH mRNA to determine the correlation of 15-PGDH level in replicate colon biopsies, in biopsies from throughout the length of the colon, in repeat biopsies taken 4 months apart, and in paired biopsies of individuals taken before and after aspirin treatment, and by Western-blot for 15-PGDH protein in mice.

Results: Colonic 15-PGDH levels varied 4.4-fold across the human population. Within individuals, 15-PGDH levels proved highly reproducible (r=0.81 in duplicate biopsies) and stable along the length of the colon, with average 15-PGDH levels deviating by only 17% from rectum to cecum. An individual's 15-PGDH levels are also highly stable over time, with a median coefficient of variation over a 4-month interval of only 12%. Last, colonic 15-PGDH levels proved resistant to alteration by aspirin, with only a 10% difference in 15-PGDH levels measured before and after aspirin treatment.

Conclusions: 15-PGDH levels vary across the population in a stable and reproducible manner, and are resistant to alteration by aspirin. 15-PGDH represents an independent target for modulation by candidate colon tumor chemopreventive agents.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aspirin / pharmacology
  • Aspirin / therapeutic use*
  • Chemoprevention
  • Colon / drug effects
  • Colon / enzymology*
  • Colonic Neoplasms / prevention & control*
  • Cyclooxygenase 1 / metabolism
  • Cyclooxygenase 2 / metabolism
  • Female
  • Humans
  • Hydroxyprostaglandin Dehydrogenases / metabolism*
  • Male
  • Protein Serine-Threonine Kinases / metabolism
  • RNA, Messenger / metabolism
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / metabolism
  • Rectum / enzymology


  • RNA, Messenger
  • Receptors, Transforming Growth Factor beta
  • Hydroxyprostaglandin Dehydrogenases
  • 15-hydroxyprostaglandin dehydrogenase
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • PTGS1 protein, human
  • PTGS2 protein, human
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II
  • Aspirin