In vitro and in vivo inhibitory effect evaluation of cyclooxygenase-2 inhibitors,antisense cyclooxygenase-2 cDNA,and their combination on the growth of human bladder cancer cells

Overexpression of cyclooxygenase (COX)-2 is associated with the progression of various malignancies, but the contribution of COX-2 expression, bioactivity or their cooperation to bladder cancer growth calls for further clarification. In this study, we investigated the inhibitory effect of COX-2 inhibitors, antisense COX-2 nucleotide, and their combination on the growth of bladder cancer cells (5637, 5637-P and 5637-AS). Suppression of either COX-2 expression or activity caused reduced cell proliferation, enhanced cell numbers in G₁ phase, and increased apoptosis; the joint suppression of COX-2 expression and bioactivity enhanced the degree of cell growth inhibition. COX-2 antisense-expressing 5637-AS tumors showed a 41.42 ± 3.08% growth inhibition as compared with 5637 controls. Oral administration of indomethacin (3 mg/kg) or celecoxib (15 mg/kg) caused tumor growth inhibition by 31.5 ± 14.87% or 83.17 ± 1.17%, respectively. When COX-2 antisense cDNA and COX-2 inhibitor celecoxib were combined, the tumor growth inhibition rate was further increased up to 88.78 ± 3.10%. These results provide evidence that celecoxib has potential therapeutic effect on bladder cancer, and the joint use of COX-2 antisense cDNA with celecoxib may improve their individual therapeutic effect, especially significantly increase the growth inhibitory effect of COX-2 antisense cDNA.