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Indomethacin reduces lung adenoma number in A/J mice
T W Moody1, J Leyton, H Zakowicz
1Cell and Cancer Biology Department Medicine Branch, National Cancer Institute, Rockville, MD 20850, USA. moodyt@bprb.nci.nih.gov
Abstract:
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.
Insights
The non-steroidal anti-inflammatory drug (NSAID) indomethacin significantly reduced lung adenoma formation in A/J mice. Indomethacin treatment also increased apoptosis and affected cyclooxygenase (COX) enzyme expression in lung tissues.
Area of Science:
- Oncology
- Pharmacology
- Immunology
Background:
- Lung adenomas are common tumors in A/J mice, often used as a model for lung cancer research.
- Non-steroidal anti-inflammatory drugs (NSAIDs) like indomethacin are known to inhibit cyclooxygenase (COX) enzymes.
- COX enzymes play a role in inflammation and cell proliferation, potentially influencing tumor development.
Purpose of the Study:
- To investigate the effects of indomethacin on urethane-induced lung adenoma formation in A/J mice.
- To examine the impact of indomethacin on apoptosis and COX enzyme expression in lung adenomas.
Main Methods:
- A/J mice were injected with urethane to induce lung adenomas.
- Indomethacin was administered to a subset of mice.
- Lung adenoma counts, apoptotic cell density, and COX-1/COX-2 expression (via immunocytochemistry and RT-PCR) were analyzed at various time points.
Main Results:
- Indomethacin significantly reduced lung adenoma incidence by 28-30% at 3, 4, and 8 months post-injection.
- A 2.9-fold increase in apoptotic cell body density was observed in lung adenomas of indomethacin-treated mice.
- Both COX-1 and COX-2 were detected in lung adenomas, bronchioli, and alveolar cells, with indomethacin potentially inhibiting their activity.
Conclusions:
- Indomethacin demonstrates chemopreventive potential against lung adenoma formation in A/J mice.
- The mechanism may involve the inhibition of COX-1 and COX-2 enzymes, leading to increased apoptosis and reduced tumor growth.
- These findings support the role of NSAIDs in modulating lung tumorigenesis.