The role of cancer stem cells in the acquired resistance to Taxol of human breast cancer cell line MCF-7

Abstract

Objective To investigate the role of cancer stem cells (CSC) in the acquired resist ance to Taxol of human breast cancer cell line MCF-7.Methods Taxol-resistant MCF-7 (MCF-7/Taxol) was established in vitro by exposure to low concentration (0.005 mg/L) and subsequently the gradually increased dose of Taxol.The proliferation and sensitivity to Taxol of MCF-7/Taxol before and after application of As2O3 were tested using methyl thiazol tetrazolium (MTT) assay.Real-time quantitative polymerase chain reaction (Real-time PCR) was employed to investigate the expression of ATP-binding cassette subfamily G member 2 (ABCG2) and sex determining region Y-box 2 (SOX-2) in wild type MCF-7 and MCF-7/Taxol cells.Results In the presence of Taxol (0.5 mg/L),the growth rate of MCF-7/ Taxol was significantly higher than the wild type MCF-7 cells (P ＜ 0.01).It was also demonstrated that MCF-7/Taxol ceils treated by Taxol developed similar proliferation to wild type MCF-7 cells in the absence of Taxol (P ＞ 0.05).The 50％ inhibitory dose (IC50) of wild type MCF-7 and MCF-7/Taxol cells to Taxol was about 0.05 mg/L and 4.2 mg/L respectively,and the resistance index was about 84.The resistance of MCF-7/Taxol ceils to Taxol was reduced after treatment of As2O3 (0.20 mg/L) with reversed multiples being 3.82 and relative reversed efficiency being 74.7％ respectively.MCF-7/Taxol cells showed elevated expression of ABCG2 and SOX-2 (P ＜0.01) in comparison with wild type MCF-7 cells.After treatment of As2O3,MCF-7/Taxol cells developed decreased levels of ABCG2 and SOX-2 (P ＜ 0.05).Conclusion CSC is a possible mechanism accounting for the acquired resistance of MCF-7/Taxol cells to Taxol. Key words: Breast cancer; Drug resistance; Taxol; Cancer stem cell