Celecoxib pre-treatment in human colorectal adenocarcinoma patients is associated with gene expression alterations suggestive of diminished cellular proliferation.
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.
Auman
James Todd
JT
UNC Institute for Pharmacogenomics and Individualized Therapy, University of North Carolina, Chapel Hill, Chapel Hill, NC 27599-7360, United States.
Church
Robert
R
Lee
Soo-Youn
SY
Watson
Mark A
MA
Fleshman
James W
JW
Mcleod
Howard L
HL
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000601:surgery; D000068579:Celecoxib; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000601:surgery; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D011300:Preoperative Care; D011720:Pyrazoles / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*; D016896:Treatment Outcome
D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib