EXPRESSION OF RECOMBINANT HUMAN CYCLOOXYGENASE ISOENZYMES IN TRANSFECTED COS-7 CELLS IN-VITRO AND INHIBITION BY TENOXICAM, INDOMETHACIN ANDASPIRIN

The recent discovery of cylooxygenase-2 (COX-2), an isoenzyme associat ed mainly with inflammation created the need to reevaluate cyclooxygen ase inhibitors with reliable screening methods. In the present study w e standardized a technique to determine the IC(50)s of cyclooxygenase inhibitors on recombinant human COX-1 and COX-2 expressed in mammalian cells and used it to study the compounds tenoxicam, aspirin and indom ethacin. The IC(50)s of aspirin, indomethacin and tenoxicam for human COX-1 were 0.41 +/- 0.07 mu g/ml, 0.008 +/- 0.003 mu g/ml, and 7.94 +/ - 3.28 mu g/ml, respectively, and for human COX-2 0.64 +/- 0.16 mu g/m l, 0.09 +/- 0.05 mu g/ml, and 10.61 +/- 1.50 mu g/ml, for aspirin, ind omethacin, and tenoxicam. Tenoxicam had the lowest IC50 hCOX-2/IC50 hC OX-1 ratio (1.34), followed by aspirin (1.53) and indomethacin (10.82) . The system described in the present study provides a simple and effi cient way to determine the specificity of NSAID inhibition for each of the human cyclooxygenase isoenzymes separately.