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
Autor: | Heliang Liu, Ling Li, Kaichun Wu, Jun Qin, Jianlin Yuan, Weijun Qin, Rong-liang Qin, Bao-Qi Chen, He Wang |
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Rok vydání: | 2008 |
Předmět: |
Male
medicine.medical_specialty DNA Complementary Indomethacin Mice Nude Apoptosis DNA Antisense Gene Expression Regulation Enzymologic chemistry.chemical_compound Mice Internal medicine Cell Line Tumor Antineoplastic Combined Chemotherapy Protocols medicine Animals Humans Cyclooxygenase Inhibitors Cell Proliferation Pharmacology Mice Inbred BALB C Sulfonamides Bladder cancer biology Cyclooxygenase 2 Inhibitors Cell growth business.industry Cancer General Medicine medicine.disease Xenograft Model Antitumor Assays Endocrinology chemistry Urinary Bladder Neoplasms Celecoxib Cyclooxygenase 2 Cancer cell Cancer research biology.protein COX-2 inhibitor Pyrazoles Cyclooxygenase Growth inhibition business medicine.drug |
Zdroj: | Biomedicinepharmacotherapy = Biomedecinepharmacotherapie. 63(3) |
ISSN: | 1950-6007 |
Popis: | 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 G(1) 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 (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. |
Databáze: | OpenAIRE |
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