Objective: To investigate the synergistic cytotoxicity of cis-dichlorodiamine platinum (DDP) and celecoxib on nasopharyngeal carcinoma TW03 cell which is resistant to DDP (TW03/DDP).
Methods: The mRNA and protein levels of lung resistance-related protein (LRP) were detected by reverse transcription PCR and Western blotting in TW03/DDP cells after (0.05-1.00) μg/mL DDP treatment. TW03/DDP clone which highly expressed LRP was transfected with siRNA targeting LRP mRNA. Nasopharyngeal carcinoma TW03 cells, TW03/DDP cells and TW03/DDP-siRNA cells were treated respectively with DDP or celecoxib or combination of the two. CCK-8 assay was performed for detecting proliferation. Annexin V-FITC/PI staining combined with flow cytometry were used for detecting apoptosis rate.
Results: Both DDP and celecoxib treatment inhibited the proliferation and induced the apoptosis of TW03 cells and TW03/DDP cells, but only celecoxib showed a significant effect on TW03/DDP cells, but not DDP. Combination of DDP and celecoxib showed a synergistic role in inducing the apoptosis of both TW03 cells and TW03/DDP cells. Meanwhile, LRP mRNA and protein levels were down-regulated in celecoxib-treated TW03/DDP cells.
Conclusion: DDP and celecoxib showed a synergistic effect on proliferation inhibition and apoptosis induction of TW03/DDP cells by down-regulating LRP mRNA and protein levels.
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