A human premetastatic colon polyp cell line, VACO-235, was used to evaluate the changes in gene expression profiles following exposure to clinically relevant concentrations of celecoxib. VACO-235 cells have been shown to progress to become weakly tumorigenic in vitro. Cultures of VAC0-235 cells were refed with medium containing the chemopreventive agent, celecoxib, at two concentrations (0.79 and 2.36 μM) or medium alone. Agent concentrations were chosen based on observed clinical plasma levels. Agents treatment times were 24, 48, and 96 hours and the treatment or control media were replenished daily. At the end of the exposures, the total RNA was isolated and, analyzed for purity and quantity using an Agilent 2100 Bioanalyzer. The samples were processed by the University of California, Irvine Core Array Facility for hybridization to Affymetrix HG-U133_PLUS_2 human arrays. Four-fold changes in expression were determined by comparing the data from the treated cultures to the time matched controls. The number of genes that showed a 4-fold reduction in expression at each time point was similar for both concentrations. The number of genes that were induced by both concentrations was greater than the ones that were inhibited. Data on specific changes in selected pathways will be presented. Both agent concentrations induced GADD45 at all time points and Reprimo at most time points indicating a block at the G2/M cell cycle checkpoint. The data suggest that changes in the patterns of gene expression following exposure to celecoxib reflect agent specific effects and that both agent concentrations are effective in altering gene expression patterns.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]