Indomethacin reduces lung adenoma number in A/J mice.
The effects of indomethacin on A/J mice were investigated. The non-steroidal antiinflammatory drug (NSAID) indomethacin reduced significantly the number of lung adenomas 3, 4 or 8 months after urethane injection by 28, 30 and 29% respectively. The density of apoptotic cell bodies increased 2.9-fold in the lung adenomas of A/J mice treated with indomethacin. By immunocytochemistry, COX-2 immunoreactivity was present in the cytosol of lung adenomas, and in epithelial cells lining the bronchioli and bronchus as well as type 2 alveolar cells. COX-1 immunostaining was similar to that of COX-2 in the lungs of urethane-injected mice treated with or without indomethacin. By RT-PCR, COX-1 and COX-2 PCR products were present in mouse lung adenomas, alveoli and bronchioli. These results suggest that indomethacin may inhibit COX-1 and COX-2 in the A/J mouse lung resulting in reduced adenoma formation.
Moody
T W
TW
Cell and Cancer Biology Department Medicine Branch, National Cancer Institute, Rockville, MD 20850, USA. moodyt@bprb.nci.nih.gov
Leyton
J
J
Zakowicz
H
H
Hida
T
T
Kang
Y
Y
Jakowlew
S
S
You
L
L
Ozbun
L
L
Zia
H
H
Youngberg
J
J
Malkinson
A
A
D000236:Adenoma / Q000139:chemically induced / Q000188:drug therapy*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis; D001980:Bronchi / Q000378:metabolism; D002273:Carcinogens; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D003600:Cytosol / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007213:Indomethacin / Q000494:pharmacology*; D007527:Isoenzymes / Q000096:biosynthesis; D008175:Lung Neoplasms / Q000139:chemically induced / Q000188:drug therapy*; D008565:Membrane Proteins; D051379:Mice; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014520:Urethane
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002273:Carcinogens; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D014520:Urethane; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; D007213:Indomethacin