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

被引:26
作者
Auman, James Todd [1 ]
Church, Robert [2 ]
Lee, Soo-Youn [1 ]
Watson, Mark A. [3 ,4 ]
Fleshman, James W. [2 ,4 ]
Mcleod, Howard L. [1 ]
机构
[1] Univ N Carolina, UNC Inst Pharmacogenom & Individualized Therapy, Chapel Hill, NC 27599 USA
[2] Washington Univ, Sch Med, Div Colorectal Surg, St Louis, MO USA
[3] Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA
[4] Siteman Canc Ctr, St Louis, MO USA
关键词
cDNA microarrays; colorectal neoplasms; celecoxib cyclooxygenase 2 inhibitors; gene expression profiling;
D O I
10.1016/j.ejca.2008.05.010
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
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 (400 mg 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. (C) 2008 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1754 / 1760
页数:7
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