Expressin of cyclooxygenase-2 in breast cancer tissues and its relationship with multidrug resistance

OBJECTIVE:To explore the role of COX-2 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-gp.METHODS:Human breast cancer MDA-MB-231 was taken as the target to investigate the effect of COX-2 inhibitor Nimesulide on the rate of apoptosis and the expressions of COX-2 and 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 Nimesulide alone or in combination with the different doses of Mitomycin.RESULTS:The cell line was treated with Mitomycin alone,and IC50 of MMC to cell line was 8.59±1.16,and the cell line was treated with 25 μmol/L Nimesulide in combination with MMC,and IC50 was 5.89±0.66,P=0.002.The cell line was treated with 50 μmol/L Nimesulide in combination with MMC,and IC50 was 3.31±0.30,P=0.003.It suggested nimesulide enhanced the chemotherapy sensitivity of mitomycin in breast cancer MDA-MB-231 in a dose-dependent manner in vitro.Flow cytometry showed nimesulide stimulated the apoptosis of MDA-MB-231 cell in dose-dependent manner(0.13±0.15→29.2±0.95),F=44.84,P=0.000.Nimesulide decreased the expressions of COX-2 and P-gp in dose-dependent manner.The expression of COX-2 was decreased from 70.37±1.98 to 9.60±2.11 and the expression of P-gp was decreased from 14.13±2.63 to 0.43±0.15,P0.05.CONCLUSIONS:Nimesulide can enhance the cytotoxicity of mitomycin in breast cancer MDA-MB-231 cell line.COX-2 is closely related to multdrug resistance,and perhaps it regulates the effect of multidrug resistance by P-gp.