Celecoxib antagonizes the cytotoxic effect of carboplatin in human esophageal cancer cells

Objective To explore the antagonizing effect of celecoxib against the cytotoxicity of carboplatin in human esophageal cancer cells.Methods The cell viability of cisplatin-resistant cell line EC109/CDDP and its parental cell line EC109exposed to carboplatin alone or carboplatin plus celecoxib was determined by MTT assay.The expression of CTR1,caspase-3activation and PARP cleavage in the exposed cells were examined by Western blotting.Caspase-3 activity and cell apoptosis after the exposure were detected with Caspase-3/7 assay and flow cytometry,respectively.The effect of celecoxib on carboplatin accumulation in the cells was measured using inductively coupled plasma mass spectrometry(ICP-MS).Results Celecoxib treatment significantly increased the IC50of carboplatin,suppressed carboplatin-induced caspase-3 and PARP cleavage and caspase-3 activity in EC109 and EC109/CDDP cells.Celecoxib also inhibited carboplatin-induced apoptosis and suppressed intracellular carboplatin accumulation in both cell lines.A combined exposure to celecoxib and carboplatin did not cause significant changes in the protein expression of CTR1.Conclusion Celecoxib antagonizes the cytotoxic effect of carboplatin and inhibits carboplatin-induced apoptosis in human esophageal cancer cells by reducing intracellular carboplatin accumulation.