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目的探讨17β-雌二醇逆转乳腺癌耐药蛋白(BCRP)介导的非典型多药耐药的机制。方法分别通过药物诱导和转基因的方法建立由BCRP和巨细胞病毒(CMV)启动子启动表达BCRP的两种耐药细胞系MCF-7/MX20和MCF-7/BCRP,将耐药细胞培养在含有17β-雌二醇的培养基中,通过细胞毒性实验,外排实验以及定量PCR观察对不同耐药细胞系的逆转作用。结果培养基中加入17β-雌二醇48h后,MCF-7/BCRP细胞中的米托蒽醌的强度明显低于MCF-7/MX20,MCF-7/BCRP细胞中BCRP mRNA的含量明显高于MCF-7/MX20。17β-雌二醇可以抑制细胞中BCRP的表达和功能,但是不能抑制MCF-7/BCRP细胞中BCRP的表达和功能。结论17β-雌二醇不是作为BCRP的底物而抑制BCRP功能的,而可能是通过调控BCRP基因的启动子发挥作用。
Objective To investigate the mechanism of 17β-estradiol reversing breast cancer resistance protein (BCRP) -mediated atypical multidrug resistance. Methods Two drug-resistant cell lines MCF-7 / MX20 and MCF-7 / BCRP expressing BCRP were constructed by BCRP and cytomegalovirus (CMV) promoters through drug-induced and transgene methods, respectively. 17β-estradiol, the reversal effect on different drug-resistant cell lines was observed by cytotoxicity test, efflux test and quantitative PCR. Results The intensity of mitoxantrone in MCF-7 / BCRP cells was significantly lower than that in MCF-7 / MX20 cells after 17β-estradiol was added to medium for 48h, and the content of BCRP mRNA in MCF-7 / BCRP cells was significantly higher than that of MCF-7 / MCF-7 / MX20.17 beta-estradiol can inhibit the expression and function of BCRP in cells, but can not inhibit the expression and function of BCRP in MCF-7 / BCRP cells. Conclusion 17β-estradiol does not inhibit BCRP function as a substrate of BCRP, but may play a role by regulating the promoter of BCRP gene.