Objective: To investigate the reversal effect of Celecoxib and Taxol on multidrug resistance (MDR) human breast cancer cells (MCF-7/Taxol) and its underlying mechanism.
Methods: After establishing the resistance cell lines of human breast cancer on Taxol (MCF-7/Taxol), the effects of the drugs on the toxicity of MCF-7/Taxol cells and the reversal effect of Celecoxib on MDR were determined by CCK-8 assay. The cells were divided into seven groups (A: MCF-7; B: MCF-7/Taxol; C: MCF-7/Taxol + 0.03 microg/mL Taxol; D: MCF-7/ Taxol + 0 .03 microg/mL Taxol + 3 microg/mL Celecoxib; E: MCF-7/Taxol + 0.03 microg/mL Taxol-6 /g/mL Celecoxib; F: MCF-7/Taxol + 3 microg/mL Celecoxib; G: MCF-7/Taxol + 6 microg/mL Celecoxib). The mRNA levels of MDR1 and BCRP in these treated cells were also determined by reverse transcription-polymerase chain reaction (RT-PCR), the protein levels of P-gp and BCRP in these treated cells were also determined by Western blot method.
Results: Compared with the Taxol control, the cytotoxicity effects was obviously increased by combination of Taxol and Celecoxib (P < 0.05). Compared with the vehicle control, Taxol up-regulated mRNA and protein levels of P-gp, whereas Celecoxib down-regulated mRNA and protein levels of P-gp and BCRP (P < 0.05).
Conclusion: Celecoxib has reversal effect on MDR in MCF-7/Taxol cells, it's possible mechanism might be related to reduce the protein expression of COX-2, the inhibition of P-gp, BCRP mRNA and protein overexpression.