The Expressin Of Cyclooxygenase-2 In Breast Cancer And The Relationship With Multidrug Resistance

Objective:To indicate the role of cox-2 take part in mediation of multidrug resistance in breast cancer by studying the effect of selective cox-2 inhibitor nimesulide on breast cancer MDA-MB-231 and its effect on the expression of P-glycoprotein.Methods:Taking human breast cancer MDA-MB-231 as targets to investigate cox-2 inhibitor nimesulide effect on rate of apoptosis and the expression of cox-2 ,P-gp by flow cytometry.MTT assay was used to compare the inhibiting rate IC50 in breast cancer MDA-MB-231 cell line treated with mitomycin alone or in combination with the different dose nimesulie.Results:Cell line was treated with mitomycin alone ,IC50 of MMC to cell line was 8.59±1.16 , cell line was treated with 25μmol/L nimesulide in combination with MMC,IC50 was 5.89±0.66, P=0.002.Cell line was treated with 50μmol/L nimesulide in combination with MMC,IC50 was 3.31±0.30,P=0.003.It suggested nimesulide could enhance chemotherapy sensitivity of mitomycin in breast cancer MDA-MB-231 and in a dose-dependent manner in vitro. Flow cytometry showed nimesulide could stimulate apoptosis of MDA-MB-231 cell and in dose-dependent manner(0.13±0.15→29.2± 0.95),F=44.84,P=0.000. Nimesulide could decrease the expression of cox-2 and P-gp, and in dose–dependent manner. The expression of cox-2 is decreased from 70.37±1.98 to 9.60±2.11,and the expression of P-gp is decreased from 14.13±2.63 to 0.43±0.15,and the expression of MRP1 is decreased from 4.60±1.45 to 0.33±0.32.Conculsion:Nimesulide could enhance cytotoxicity of mitomycin in breast cancer MDA-MB-231 cell line .cox-2 is closely related with multdrug resistance ,and perhaps it regulates effect of multidrug resistance by P-gp.