Celecoxib antagonizes the cytotoxic effect of carboplatin in human esophageal cancer cells / 南方医科大学学报

ABSTRACT

<p><b>OBJECTIVE</b>To explore the antagonizing effect of celecoxib against the cytotoxicity of carboplatin in human esophageal cancer cells.</p><p><b>METHODS</b>The cell viability of cisplatin-resistant cell line EC109/CDDP and its parental cell line EC109 exposed to carboplatin alone or carboplatin plus celecoxib was determined by MTT assay. The expression of CTR1, caspase-3 activation 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).</p><p><b>RESULTS</b>Celecoxib treatment significantly increased the IC50 of 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.</p><p><b>CONCLUSION</b>Celecoxib antagonizes the cytotoxic effect of carboplatin and inhibits carboplatin-induced apoptosis in human esophageal cancer cells by reducing intracellular carboplatin accumulation.</p>