title: Celecoxib antagonizes the cytotoxic effect of cisplatin in human gastric cancer cells by decreasing intracellular cisplatin accumulation.
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.
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
authors.forename: Minghui
authors.initials: M
authors.lastname: Chen
authors.forename: Le
authors.initials: L
authors.lastname: Yu
authors.forename: Chunping
authors.initials: C
authors.lastname: Gu
authors.forename: Desheng
authors.initials: D
authors.lastname: Zhong
authors.forename: Shuguang
authors.initials: S
authors.lastname: Wu
authors.forename: Shuwen
authors.initials: S
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001692:Biological Transport / Q000187:drug effects; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D000068579:Celecoxib; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000378:metabolism / Q000494:pharmacology*; D000079923:Copper Transporter 1; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D018736:DNA Adducts / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004347:Drug Interactions; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D007424:Intracellular Fluid / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011720:Pyrazoles / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D000096926:Benzenesulfonamides
chemical_list: D000970:Antineoplastic Agents; D027682:Cation Transport Proteins; D000068579:Celecoxib; D002945:Cisplatin; D000079923:Copper Transporter 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D018736:DNA Adducts; D015232:Dinoprostone; D011720:Pyrazoles; D013449:Sulfonamides; C119130:4-(5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide; D000096926:Benzenesulfonamides; C490079:SLC31A1 protein, human; C496540:PTGS2 protein, human