Indomethacin inhibits the accumulation of tumor cells in mouse lungs and subsequent growth of lung metastases.
BACKGROUND
The interaction of cancer cells with blood cells and cell wall components evokes inflammatory responses and is a critical event in the metastatic process. Indomethacin is a potent inhibitor of the cyclooxygenase (COX) enzymes and has previously been shown to decrease the growth of primary tumors in vivo. Proinflammatory prostaglandins produced by the two COX enzymes may also play a role in the development of metastases.


METHODS
To directly address this question, we tested the effect of indomethacin on the accumulation of circulating [(3)H]-uridine-labeled tumor cells in the lungs and on the subsequent development of lung tumors.


RESULTS
We found that inhibition of COX activity in the recipient mice prior to the injection of tumor cells decreased the percentage of the cells arrested in the lungs. This effect was highly significant since it subsequently led to substantial attenuation of lung metastasis development.


CONCLUSIONS
These data thus demonstrate the antimetastatic effect of indomethacin through a mechanism which involves a reduction in tumor cell uptake by the lungs.
Levin
G
G
Department of Biochemistry, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
Kariv
N
N
Khomiak
E
E
Raz
A
A
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015197:Carcinogenicity Tests / Q000379:methods; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy / Q000556:secondary; D002455:Cell Division / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects; D014018:Tissue Distribution; D014529:Uridine / Q000493:pharmacokinetics
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011451:Prostaglandin-Endoperoxide Synthases; D014529:Uridine; D007213:Indomethacin