THE STUDY OF THE MECHANISM OF 17?-ESTRADIOL ON REVERSAL OF THE BREAST CANCER RESISTANT PROTEIN-MEDIATED MULTIDRUG RESISTANCE / 解剖学报

ABSTRACT

Objective To explore the mechanism of the reversal of breast cancer resistant protein-mediated multidrug resistance by 17?-estradiol. Methods Two BCRP expressing cell lines of MCF-7/MX20 and MCF-7/BCRP were established in which breast canrcer resistant protein(BCRP) was promoted by BCRP promoter and cytomegalovirus(CMV) promoter respectively.These drug resistant cell lines were cultured in medium containing 17?-estradiol.Fourty-eight hours later,cytotoxicity assay,mitoxantrone efflux assays,quantitative RT-PCR were performed to observe the reversal function of BCRP by 17?-estradiol on MCF-7/MX20 and MCF-7/BCRP respectively. Results After being treated with 17?-estradiol,the intensity of mitoxantrone in MCF-7/BCRP was weaker than that in MCF-7/MX20 and the BCRP mRNA level in MCF-7/BCRP was high than that in MCF-7/MX20.The results of these experiments revealed that 17?-estradiol could reverse the BCRP mediated multidrug resistance(MDR) in MCF-7/MX20 cells but not in MCF-7/BCRP ones.Conclusion 17?-estradiol may reverse the phenotype of BCRP through regulation of the promoter of BCRP gene but not acted as the substrate of BCRP.