Drug Resistant Breast Cancer Cell Line Displays Cancer Stem Cell Phenotype and Responds Sensitively to Epigenetic Drug SAHA

耐药乳腺癌细胞系表现出癌症干细胞表型并对表观遗传药物 SAHA 有敏感反应

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作者:Shan Lu, Vinod Labhasetwar

Abstract

Cancer stem cell (CSC) population in solid human breast tumor was identified by CD44(+)/CD24(-) phenotype, characterized by high tumorigenicity, invasiveness and drug resistance. In this study, we characterized drug resistant breast cancer cell line-MCF-7/Adr and a number of breast cancer cell lines using flow cytometry, immunofluorescence, mammosphere formation assay and migration assay, examining their CSC immunophenotypes, presence of CSC proteins, tumorigenicity in vitro and migratory rates, respectively. Our results show that MCF-7/Adr cells uniformly display CSC characteristics yet retain low migratory rate. They are also able to self-renew and differentiate under floating culture conditions. Furthermore, MCF-7/Adr is selectively sensitive to epigenetic drug, suberoylanilide hydroxamic acid (SAHA), losing drug resistance and changes morphology yet retaining CSC immunophenotypes. In conclusion, we show that resistant breast cancer cell line MCF-7/Adr demonstrates uniform CSC like characteristics and are sensitive to epigenetic drug treatment.

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