Abstract
Cisplatin is a chemotherapeutic drug widely used for the treatment of gastric cancer. The benefit of including COX-2-selective inhibitors in cisplatin-based regimens on anti-cancer effect remains uncertain. In the present study, celecoxib and SC-236 antagonized cisplatin-induced cytotoxicity and apoptosis, whereas indomethancin and nimesulide exerted no effect, implying a COX-2-independent mechanism. Celecoxib decreased whole-cell cisplatin accumulation and DNA platination, resulting from reduced influx. In addition, combined treatment did not elicit greater antitumor activity than cisplatin or celecoxib monotherapy in vivo in a gastric xenograft model. Therefore, treatment strategies with celecoxib in combination with cisplatin should act cautiously.
Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents / metabolism
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Antineoplastic Agents / pharmacology*
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Apoptosis / drug effects
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Biological Transport / drug effects
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Cation Transport Proteins / genetics
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Cation Transport Proteins / metabolism
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Celecoxib
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Cell Line, Tumor
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Cell Survival / drug effects
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Cisplatin / metabolism
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Cisplatin / pharmacology*
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Copper Transporter 1
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Cyclooxygenase 2 / metabolism
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Cyclooxygenase 2 Inhibitors / pharmacology*
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DNA Adducts / metabolism
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Dinoprostone / metabolism
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Drug Interactions
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Female
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Gene Expression / drug effects
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Humans
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Inhibitory Concentration 50
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Intracellular Fluid / metabolism
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Pyrazoles / pharmacology*
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Sulfonamides / pharmacology*
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Tumor Burden / drug effects
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Xenograft Model Antitumor Assays
Substances
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4-(5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide
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Antineoplastic Agents
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Cation Transport Proteins
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Copper Transporter 1
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Cyclooxygenase 2 Inhibitors
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DNA Adducts
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Pyrazoles
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SLC31A1 protein, human
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Sulfonamides
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Cyclooxygenase 2
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PTGS2 protein, human
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Celecoxib
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Dinoprostone
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Cisplatin