Celecoxib antagonizes the cytotoxicity of oxaliplatin in human esophageal cancer cells by impairing the drug influx

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• 作者：Yi Kong ^{kongyijk@126.com" class="auth_mail" title="E-mail the corresponding author} ; Chunping Gu ^{pingchungu_2006@126.com" class="auth_mail" title="E-mail the corresponding author} ; Desheng Zhong ^{dersonzhong@163.com" class="auth_mail" title="E-mail the corresponding author} ; Xuyan Zhao ^{984623086@qq.com" class="auth_mail" title="E-mail the corresponding author} ; Qinghuan Lin ^{443853020@qq.com" class="auth_mail" title="E-mail the corresponding author} ; Keng Wang ^{380292021@qq.com" class="auth_mail" title="E-mail the corresponding author} ; Tianrong Xun ^{727582649@qq.com" class="auth_mail" title="E-mail the corresponding author} ; Le Yu ; ^{yulezy@smu.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Shuwen Liu ; ^{liusw@smu.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：COX-2 ; cyclooxygenase-2 ; CTR1 ; copper transporter 1 ; FCM ; flow cytometry ; FITC ; fluorescein isothiocyanate ; ICP-MS ; inductively coupled plasma mass spectroscopy ; MTT ; 3-(4 ; 5-dimethylthiazol-2-yl)-2 ; 5-diphenyltetrazolium bromide ; NSAIDs ; nonsteroidal anti-inflammatory drugs ; OCT ; organic cation transporter ; PARP ; poly(ADP-ribose) polymerase ; PGE2 ; prostaglandin E2 ; PI ; propidium iodide ; SC-236 ; 4-[5-(4-chlorophenyl)-3-(trifluoro-methyl)-1H-pyrazol-1-yl]benzenesulfonamide ; SLCs ; solute carriers ; T
• 刊名：European Journal of Pharmaceutical Sciences
• 出版年：2016
• 出版时间：1 January 2016
• 年：2016
• 卷：81
• 期：Complete
• 页码：137-148
• 全文大小：2377 K

文摘

It has been demonstrated that COX-2-selective inhibitor celecoxib shows synergy with oxaliplatin for suppressing tumor growth. However, the benefit of adding celecoxib to oxaliplatin-based regimen in human esophageal cancer is largely unknown. In the present study, we demonstrated that celecoxib antagonized oxaliplatin-induced cytotoxicity and apoptosis independent of COX-2 inhibition in human esophageal cancer cells. Celecoxib decreased cellular oxaliplatin accumulation and Pt-DNA adduction formation due to reduced drug influx. Celecoxib alone or combined with oxaliplatin substantially reduced the expression of organic cation transporter 2 (OCT2). To this end, OCT2 knockdown was sufficient to reduce oxaliplatin uptake, connecting OCT2 expression to oxaliplatin accumulation. Moreover, oxaliplatin combined with celecoxib also showed no beneficial effect when compared with monotherapy in esophageal cancer cell-xenografted nude mice. To conclude, our data provide evidence that the addition of celecoxib to oxaliplatin-containing regimens for patients with OCT2-expressing cancers should be cautious.