中国全科医学2011,Vol.14Issue(24):2749-2754,6.
多西紫杉醇对乳腺癌干细胞的作用研究
Effects of Docetaxel on Human Breast Cancer Stem Cells
摘要
Abstract
Objective This study aims to evaluate the effects of a semisynthetic member of the taxoid class of antineoplastic agents, docetaxel, on breast CSCs of primary breast cancer cells and two breast cancer cell lines ( MCF - 7, MDA - MB-231 ) in vitro with the hope to provide reference for the stem cell - based drug treatment of breast cancer. Methods We sorted CD44+ , CD24-/low, ESA+ cells as breast CSCs by flow cytometry from primary breast cancer cells, breast cancer cell lines MCF -7 and MDA - MB - 231. And then the three CSCs were treated with different concentrations of docetaxel ( 10 nmol/L, 100 nmol/L, 1 μmol/L, 10 μmol/L, 100 μmol/L ). The inhibition effects of the drug on different breast CSCs were quantified by methyl thiazolyl tetrazolium ( MTT ) assay. Apoptosis and distribution of cell cycles were examined with flow cytometry. Results Proportion of stem cells in the three cell lines, primary breast cancer cells. MCF - 1, and MDA - MB - 231, were ( 0.50 ±0.26 )%, ( 1.40 ±0.26 )%, and ( 1.63±0.32 )% respectively. It was showed hy MTT assay that all the studied cell lines were docetaxel - resistant to some extent : IC50 for unclassified cells and for stem cells were 34 nmol/L and 12.422 μmol/L for MDA - MB -231 cells ( P < 0.01 ), 31 nmol/L and 8.357 μmol/L for MCF-7 cells ( P <0.01 ), 51 nmol/L and 17.688 μmol/L for primary breast cancer cells ( P < 0.01 ). The inhibition effects of docetaxel on cancer cells were dose - dependent.Docetaxel caused cell cycle arrest at S and G2/M phases in the studied cell lines and the early apoptosis rates observed were time-dependent. Conclusion Docetaxel exhibits growth inhibition effects on breast CSCs in vitro, which are hoth dose - dependent and time - dependent, and reduces the tumorigenicity of breast CSCs.关键词
乳腺肿瘤/干细胞/多西紫杉醇Key words
Breast neoplasms/ Stem cells/ Docetaxel分类
医药卫生引用本文复制引用
钱钧强,张霄蓓,马懿,郝晓甍,张晟..多西紫杉醇对乳腺癌干细胞的作用研究[J].中国全科医学,2011,14(24):2749-2754,6.基金项目
天津市科技支撑重大项目(09ZCZDSF04000) (09ZCZDSF04000)