铁螯合剂通过抑制P-gp的表达促进乳腺癌化疗增敏  

Iron Chelator Promotes Breast Cancer Chemo-resensitization through Down-regulation of P-glycoprotein

作　　者：程曼 何坤 李晶[1] 刘苹[1,2] 

机构地区：[1]上海交通大学生物医学工程学院,上海200240 [2]上海交通大学Med-X研究院,上海200030

出　　处：《生物医学工程学进展》2017年第3期135-139,共5页Progress in Biomedical Engineering

摘　　要：多重耐药和肿瘤转移是治愈肿瘤的两大障碍。上皮间质转化作为肿瘤转移的早期事件与化疗耐药相关。有研究表明铁促进乳腺癌的发展,但是铁在乳腺癌化疗耐药中的作用尚不明确。经研究发现乳腺癌化疗耐药细胞系MCF-7/Adr细胞内的铁含量明显高于化疗敏感细胞MCF-7,并且ABC转运体P-gp和间质表型标志物的表达受细胞内铁水平的调控。铁螯合剂DFO靶向细胞内的铁会抑制P-gp的表达及药物泵出功能,从而产生化疗增敏作用。因此靶向细胞内的铁可以作为克服乳腺癌多重耐药的潜在手段。Multidrug resistance and tumor metastasis are two major obstacles in successful treatment of cancer. Epithelial - mesenchymal transition （ EMT） as early event in cancer metastasis has been believed to induce chemoresistance. Some studies support that iron promotes the development of breast cancer. However, the role of i- ron in breast cancer chemoresistance has not been determined. In the present study, we found that intracellular iron concentration in chemoresistant breast cancer cell line MCF -7/Adr was much higher as compared to drug sensitive cell line MCF - 7. The expression of ABC transporter P - glycoprotein and mesenchymal markers was regulated by intracellular iron level in MCF - 7/Adr. Targeting iron by iron chelator Deferoxamine （DFO） exerted chemo - re-sensitization effect mediated by inhibition of P - gp expression and blocking the drug efflux function. Our findings suggested it would be appropriate to continue to investigate targeting iron as a promising strategy to overcome che-moresistance.

关 键 词：乳腺癌 化疗耐药 铁螯合剂 P-GP 

分 类 号：R737.9[医药卫生—肿瘤]