Indomethacin and poly I:C in the inhibition of carcinogen-induced bladder cancer in an experimental animal model.
Fischer rats, in whom superficial transitional cell cancers of the urinary bladder were induced by the carcinogen N-[4-(5- nitrofuryl )-2-thiazolyl] formamide, were inoculated intraperitoneally with either phosphate buffered saline, indomethacin (a prostaglandin synthetase inhibitor), poly I:C (an interferon inducer), or indomethacin together with poly I:C. While indomethacin alone appeared to have a significant albeit variable inhibitory effect on tumor size, poly I:C had a far more pronounced significant inhibitory effect. The combination of poly I:C and indomethacin together, however, led to the greatest inhibition in tumor growth, and in some instances, to tumor regression. Splenic lymphocytes from the same animals demonstrated enhanced natural cytotoxicity after treatment with poly I:C. Surprisingly, levels of natural cytotoxicity seen in animals treated with indomethacin and poly I:C together were lower than those seen with poly I:C alone. No enhancement of cytotoxicity could be demonstrated in vitro in lymphocytes from indomethacin-treated animals. Macrophages were also treated in this system under identical conditions. However, the activity of macrophages alone and of macrophages and lymphocytes together did not appear to be modified either by indomethacin alone or by the combination of prostaglandin synthetase inhibition and interferon induction together, the combination of which in vivo was suggested to be most effective in controlling tumor progression. Further studies to determine timing of these interactions and doses of immune response modifiers in order to characterize mechanisms possibly at work in modifying tumor growth in this system therefore seem highly indicated.
D000818:Animals; D003602:Cytotoxicity, Immunologic; D005200:FANFT / Q000037:antagonists & inhibitors; D007213:Indomethacin / Q000494:pharmacology*; D007372:Interferons / Q000378:metabolism; D008297:Male; D011070:Poly I-C / Q000494:pharmacology*; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000188:drug therapy*
D011453:Prostaglandins; D005200:FANFT; D007372:Interferons; D011070:Poly I-C; D007213:Indomethacin