A cell-based assay is provided for screening substances for the capacity to inhibit COX-2 activity. The assay utilizes as a screening reagent a cell line which has been engineered to achieve constitutive or inducible expression of COX-2. In one embodiment, the cells express a GTPase-deficient, constitutively-activated mutant form of the -subunit of protein G12 which induces the production of arachidonic acid and COX-2. Decreased cell proliferation in the presence of test substance indicates that the substance has COX-2 inhibitory activity.