TITLE

Down-Regulation of PGE2 by Physiologic Levels of Celecoxib is not Sufficient to Induce Apoptosis or Inhibit Cell Proliferation in Human Colon Carcinoma Cell Lines

AUTHOR(S)
Shahar Lev-Ari; Dina Kazanov; Eliezer Liberman; Rami Ben-Yosef; Nadir Arber
PUB. DATE
April 2007
SOURCE
Digestive Diseases & Sciences;Apr2007, Vol. 52 Issue 4, p1128
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Abstract  This study was performed to evaluate whether down-regulation of prostaglandin E2(PGE2) synthesis by celecoxib treatment is associated with inhibition of cell growth in human colon carcinoma cell lines. Physiologic concentrations of celecoxib (5–10 μM) inhibited 80% to 90% of PGE2production in HT-29 cells that express high levels of COX-2 protein. In these concentrations, celecoxib had a minor inhibitory effect (20–30%) on cell growth. There was a significant change in induction of apoptosis only at higher concentrations of celecoxib (>20μM). Treatment by low concentrations of celecoxib did not alter the levels of COX-1, β-catenin, P27, Bcl-2, and Bcl-x proteins. The effect of celecoxib on cell growth inhibition was higher on the COX-2-positive HT-29 cell line (IC50=20μM) than on the COX-2 deficient SW-480 cell line (IC50=35μM). In conclusion, inhibition of PGE2synthesis is an early, but not sufficient, step in the mechanism of celecoxib-mediated cell growth inhibition. These results support the need for additional evaluation of independent COX-2 pathways of celecoxib in chemoprevention of CRC.
ACCESSION #
24518473

 

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