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Celecoxib treatment alters the gene expression profile of normal colonic mucosa

Oleg K Glebov1, Luz M Rodriguez, Patrick Lynch

  • 1Genetics Branch, Center for Cancer Research, National Naval Medical Center, Bethesda, Maryland, USA.

Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology
|July 13, 2006
PubMed

Insights

Celecoxib, a cyclooxygenase-2 inhibitor, alters gene expression in the healthy colon of hereditary nonpolyposis colon cancer patients. This study reveals its impact on immune response and cellular signaling pathways.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacogenomics

Background:

  • Hereditary nonpolyposis colon cancer (HNPCC) patients have an increased risk of colorectal cancer.
  • Selective cyclooxygenase-2 (COX-2) inhibitors, like celecoxib, are being investigated for chemoprevention in HNPCC.
  • Understanding the molecular effects of celecoxib in normal colonic mucosa is crucial for assessing its potential benefits and risks.

Purpose of the Study:

  • To evaluate the impact of celecoxib on gene expression in the normal colonic mucosa of HNPCC patients and gene carriers.
  • To identify specific biological pathways affected by celecoxib treatment.
  • To assess the potential of gene expression patterns to predict treatment response.

Main Methods:

  • A randomized, placebo-controlled phase I/II multicenter trial was conducted.
  • Gene expression analysis was performed using cDNA array technology on colonic biopsies before and after 12 months of treatment with celecoxib or placebo.
  • Overrepresentation analysis across Gene Ontology categories was used to identify targeted biological processes.

Main Results:

  • Celecoxib treatment (200 and 400 mg) significantly altered the expression of over 1,400 genes in healthy colon tissue compared to placebo.
  • Gene expression patterns could correctly classify 23 out of 25 patient biopsy pairs post-treatment.
  • Key affected biological processes include immune response, inflammatory reactions, cell signaling, cell adhesion, stress response, transforming growth factor-beta signaling, and apoptosis regulation.

Conclusions:

  • Celecoxib induces significant changes in gene expression in the healthy colon of HNPCC patients.
  • These changes suggest that celecoxib may modulate immune responses, inflammation, cell signaling, and apoptosis.
  • The findings provide insights into the molecular mechanisms underlying celecoxib's effects and its potential role in HNPCC chemoprevention.

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