Celecoxib decreases Ki-67 proliferative index in active smokers

Clin Cancer Res. 2006 Jan 1;12(1):314-20. doi: 10.1158/1078-0432.CCR-05-1440.

Abstract

Purpose: This study evaluated the feasibility of cyclooxygenase-2 (COX-2) inhibition for lung cancer chemoprevention. We hypothesized that treatment with oral Celecoxib, a selective COX-2 inhibitor, would favorably alter the biomarkers of lung cancer risk as measured by the Ki-67 proliferative labeling index (Ki-67 LI).

Experimental design: Twenty active heavy smokers were enrolled into a pilot study and treated with Celecoxib for 6 months. Bronchoscopies with bronchial biopsies were done before and after 6 months of Celecoxib treatment. H&E stain for histologic grading and immunohistochemical examination for Ki-67 LI, COX-2, and survivin were carried out on serially matched biopsy samples to determine responses to treatment.

Results: Treatment with Celecoxib significantly reduced Ki-67 LI in smokers by 35% (P = 0.016), and increased the expression of nuclear survivin by 23% (P = 0.036) without significantly changing that of cytoplasmic survivin.

Conclusions: Our findings suggest that oral Celecoxib may be capable of modulating the proliferation indices and apoptotic balance in bronchial tissue of active smokers.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Bronchi / drug effects*
  • Bronchi / metabolism
  • Celecoxib
  • Cyclooxygenase 2 / biosynthesis
  • Cyclooxygenase 2 / drug effects
  • Cyclooxygenase 2 Inhibitors / therapeutic use*
  • Female
  • Humans
  • Immunohistochemistry
  • Inhibitor of Apoptosis Proteins
  • Ki-67 Antigen / drug effects
  • Lung Neoplasms / prevention & control*
  • Male
  • Microtubule-Associated Proteins / biosynthesis
  • Microtubule-Associated Proteins / drug effects
  • Middle Aged
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / drug effects
  • Pilot Projects
  • Pyrazoles / therapeutic use*
  • Smoking / adverse effects*
  • Sulfonamides / therapeutic use*
  • Survivin

Substances

  • BIRC5 protein, human
  • Cyclooxygenase 2 Inhibitors
  • Inhibitor of Apoptosis Proteins
  • Ki-67 Antigen
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Pyrazoles
  • Sulfonamides
  • Survivin
  • Cyclooxygenase 2
  • Celecoxib