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Randomized Controlled Trial
. 2008 Aug;44(12):1754-60.
doi: 10.1016/j.ejca.2008.05.010. Epub 2008 Jul 22.

Celecoxib pre-treatment in human colorectal adenocarcinoma patients is associated with gene expression alterations suggestive of diminished cellular proliferation

James Todd Auman  1 , Robert Church, Soo-Youn Lee, Mark A Watson, James W Fleshman, Howard L Mcleod
Affiliations
Randomized Controlled Trial

Celecoxib pre-treatment in human colorectal adenocarcinoma patients is associated with gene expression alterations suggestive of diminished cellular proliferation

James Todd Auman et al. Eur J Cancer. 2008 Aug.

Abstract

Cancer cells treated with the cyclooxygenase-2 inhibitor celecoxib show growth inhibition and induced apoptosis. This study was conducted to determine if the same processes are relevant to celecoxib's effects on human colorectal adenocarcinomas treated in vivo. A cohort of 23 patients with primary colorectal adenocarcinomas was randomised to receive a 7-d course of celecoxib (400mg b.i.d.) or no drug prior to surgical resection. Gene expression profiling was performed on resected adenocarcinomas from the cohort of patients. Using fold change (>1.5) and p-value (<0.05) cut-offs, 190 genes were differentially expressed between adenocarcinomas from patients receiving celecoxib and those that did not. The celecoxib pre-treated samples showed decreased expression levels in multiple genes involved in cellular lipid and glutathione metabolism; changes associated with diminished cellular proliferation. Celecoxib pre-treatment for 7 d in vivo is associated with alterations in colorectal adenocarcinoma gene expression which are suggestive of diminished cellular proliferation.

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Conflict of interest statement

Conflict of Interest Statement: All of the authors state that they do not have any conflicts of interest.

Figures

Figure 1
Figure 1. Clustering of gene expression in colorectal adenocarcinoma patients
Unsupervised hierarchical clustering was performed on all samples using 10,083 genes with a normalized expression standard deviations greater than 0.04. The dendrogram indicates that the samples do not cluster based solely on any of the recorded phenotypic characteristics.
Figure 2
Figure 2. Differentially expressed genes associated with celecoxib pre-treatment
2A: Volcano plot of gene expression changes between colorectal adenocarcinomas from patients pre-treated and not pre-treated with celecoxib. 2B: Clustering using the 190 differentially expressed genes. Red indicates increased expression; green indicates decreased expression and black indicates no difference.
Figure 2
Figure 2. Differentially expressed genes associated with celecoxib pre-treatment
2A: Volcano plot of gene expression changes between colorectal adenocarcinomas from patients pre-treated and not pre-treated with celecoxib. 2B: Clustering using the 190 differentially expressed genes. Red indicates increased expression; green indicates decreased expression and black indicates no difference.
See this image and copyright information in PMC

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