Increased cyclooxygenase-2 Levels in Carcinogen-Induced Rat Colonic Tumors

Gastroenterology. 1996 Apr;110(4):1259-62. doi: 10.1053/gast.1996.v110.pm8613017.

Abstract

Background & aims: Multiple studies show that continuous use of nonsteroidal anti-inflammatory drugs (NSAIDs) lowers the risk of colon cancer in humans and carcinogen-treated rodents. One target for NSAIDs is cyclooxygenase (COX), and two isoforms of this enzyme have been identified: COX-1 and COX-2. The present study was undertaken to determine if there is differential expression of COX in colonic tumors in azoxymethane-treated rats.

Methods: COX-1 and COX-2 messenger RNA levels were determined by Northern blot analysis of total RNA isolated from colonic tumors and normal adjacent mucosa. COX-2 protein levels were determined by Western blotting analysis. Quantitation of relative band densities was performed using standard densitometry scanning techniques.

Results: There was a marked increase in COX-2 RNA levels in six of six colonic tumors compared with paired normal mucosa. In contrast, there was equivalent intensity of the COX-1 RNA transcript between the normal mucosa and tumor in all of the specimens examined. Western blotting analysis showed an increase in the level of the COX-2 protein in four of five of the colonic tumor samples.

Conclusions: COX-2 but not COX-1 gene expression is markedly elevated in most colonic tumors examined in azoxymethane-treated rodents. COX-2 may provide a target for chemopreventive strategies for colorectal cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Azoxymethane
  • Blotting, Northern
  • Blotting, Western
  • Colon / enzymology
  • Colonic Neoplasms / chemically induced
  • Colonic Neoplasms / enzymology*
  • Cyclooxygenase 2
  • Intestinal Mucosa / enzymology
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • Male
  • Prostaglandin-Endoperoxide Synthases / genetics
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Inbred F344

Substances

  • Isoenzymes
  • RNA, Messenger
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Azoxymethane