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Celecoxib antagonizes the cytotoxicity of oxaliplatin in human esophageal cancer cells by impairing the drug influx
- Source :
- European Journal of Pharmaceutical Sciences. 81:137-148
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- 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.
- Subjects :
- musculoskeletal diseases
0301 basic medicine
Esophageal Neoplasms
Organic Cation Transport Proteins
Organoplatinum Compounds
Cell Survival
Mice, Nude
Pharmaceutical Science
Antineoplastic Agents
Apoptosis
Pharmacology
03 medical and health sciences
0302 clinical medicine
Cell Line, Tumor
health services administration
Antineoplastic Combined Chemotherapy Protocols
Animals
Humans
Medicine
Drug Interactions
RNA, Small Interfering
Cytotoxicity
neoplasms
Gene knockdown
Organic cation transport proteins
TUNEL assay
Cyclooxygenase 2 Inhibitors
biology
business.industry
Organic Cation Transporter 2
Esophageal cancer
medicine.disease
digestive system diseases
Tumor Burden
Oxaliplatin
stomatognathic diseases
030104 developmental biology
Celecoxib
030220 oncology & carcinogenesis
biology.protein
Female
business
medicine.drug
Subjects
Details
- ISSN :
- 09280987
- Volume :
- 81
- Database :
- OpenAIRE
- Journal :
- European Journal of Pharmaceutical Sciences
- Accession number :
- edsair.doi.dedup.....8aa06371cdd9ff552a33184f445e3432