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 - 02/03/09
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Abstract |
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 (3mg/kg) or celecoxib (15mg/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.
Le texte complet de cet article est disponible en PDF.Keywords : COX-2 antisense cDNA, COX-2 inhibitor, Therapeutic effect
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Vol 63 - N° 3
P. 241-248 - mars 2009 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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