Celecoxib decreases Ki-67 proliferative index in active smokers.
OBJECTIVE
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).


METHODS
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.
Mao
Jenny T
JT
Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90095-1690, USA. jmao@mednet.ucla.edu
Fishbein
Michael C
MC
Adams
Bradley
B
Roth
Michael D
MD
Goodglick
Lee
L
Hong
Longsheng
L
Burdick
Marie
M
Strieter
E Robert M
ER
Holmes
Carmack
C
Tashkin
Donald P
DP
Dubinett
Steven M
SM
D000368:Aged; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism; D000068579:Celecoxib; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D019394:Ki-67 Antigen / Q000187:drug effects; D008175:Lung Neoplasms / Q000517:prevention & control*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000187:drug effects; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000187:drug effects; D010865:Pilot Projects; D011720:Pyrazoles / Q000627:therapeutic use*; D012907:Smoking / Q000009:adverse effects*; D013449:Sulfonamides / Q000627:therapeutic use*; D000077022:Survivin
C107489:BIRC5 protein, human; D052246:Cyclooxygenase 2 Inhibitors; D051034:Inhibitor of Apoptosis Proteins; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011720:Pyrazoles; D013449:Sulfonamides; D000077022:Survivin; D051546:Cyclooxygenase 2; D000068579:Celecoxib