Abstract | PURPOSE: MATERIALS AND METHODS: Cytotoxicity was determined by the microculture tetrazolium dye assay. RESULTS: Combination treatment of T24 bladder cancer cells with JTE-522 and cis-diamminedichloroplatinum (II) (CDDP) resulted in a synergistic cytotoxic effect. Synergy achieved in cytotoxicity with JTE-522 and CDDP was shown to be due to apoptosis. Treatment of T24 cells with JTE-522 decreased expression of the anti-apoptotic molecule Bcl-2. The in vivo significant growth inhibitory effect of JTE-522 and CDDP against the T24 line heterotransplanted in SCID mice was also observed. CONCLUSIONS: This study demonstrates that combination treatment of bladder cancer cells with the selective COX-2 inhibitor JTE-522 and CDDP results in synergistic cytotoxicity and apoptosis in vitro and in vivo. These findings support the potential clinical application of a combination of JTE-522 and CDDP for the treatment of bladder cancer as a new form of therapy with more selective cytotoxicity and fewer collateral side effects.
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Authors | Yoichi Mizutani, Hiroyuki Nakanishi, Yong Nan Li, Nodoka Sato, Akihiro Kawauchi, Tsuneharu Miki |
Journal | The Journal of urology
(J Urol)
Vol. 172
Issue 4 Pt 1
Pg. 1474-9
(Oct 2004)
ISSN: 0022-5347 [Print] United States |
PMID | 15371874
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 4-(4-cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamide
- Antineoplastic Agents
- Benzenesulfonates
- Cyclooxygenase Inhibitors
- Oxazoles
- Proto-Oncogene Proteins c-bcl-2
- Cisplatin
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Topics |
- Animals
- Antineoplastic Agents
(pharmacology)
- Apoptosis
(drug effects)
- Benzenesulfonates
(pharmacology)
- Carcinoma, Transitional Cell
(pathology)
- Cell Division
(drug effects)
- Cell Line, Tumor
- Cell Survival
(drug effects)
- Cisplatin
(pharmacology)
- Cyclooxygenase Inhibitors
(pharmacology)
- Drug Synergism
- Female
- Humans
- Mice
- Mice, SCID
- Neoplasm Transplantation
- Oxazoles
(pharmacology)
- Proto-Oncogene Proteins c-bcl-2
(antagonists & inhibitors)
- Tumor Cells, Cultured
(drug effects, pathology)
- Tumor Stem Cell Assay
- Urinary Bladder Neoplasms
(pathology)
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