肿瘤干细胞在人乳腺癌细胞株MCF-7耐紫杉醇效应中的作用  

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

作　　者：韩娜[1] 穆永慧[3] 张庆[2] 

机构地区：[1]郑州大学第二附属医院肿瘤科,450014 [2]郑州大学第二附属医院妇产科,450014 [3]新乡医学院病理生理学教研室

出　　处：《中华实验外科杂志》2014年第7期1482-1484,共3页Chinese Journal of Experimental Surgery

摘　　要：目的 观察肿瘤干细胞（CSC）在人乳腺癌细胞株MCF-7对紫杉醇（Taxol）产生获得性耐药中的作用。方法 采用低浓度加量（起始浓度为0.005 mg/L）持续诱导法诱导产生人乳腺癌耐Taxol细胞株MCF-7/Taxol,噻唑蓝（MTT）法检测MCF-7/Taxol对Taxol的敏感性。实时定量聚合酶链反应（Real-time PCR）检测三磷酸腺苷结合转运蛋白G超家族成员2（ABCG2）和性别决定区Y-框蛋白2（SOX-2）的表达。结果 亲本株和耐药株细胞对Taxol的半数抑制浓度（IC50）值分别为0.05 mg/L和4.2 mg/L,耐药指数为84。0.20 mg/L的As2O2降低了耐药株对Taxol的耐药性,逆转倍数为3.82,相对逆转效率为74.7%。耐药株细胞ABCG2和SOX-2的表达显著升高（P〈0.01）。As2O3处理后,ABCG2和SOX-2的表达显著下降（P〈0.05）。结论 CSC有可能是人乳腺癌细胞株MCF-7对Taxol产生耐药的机制之一。Objective To investigate the role of cancer stem cells （CSC） in the acquired resistance 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 As203 were tested using methyl thiazol tetrazolium （IVITY） 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 rag/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 cells treated by Taxol developed similar proliferation to wild type MCF-7 cells in the absence of Taxol （P 〉 0. 05）. The 50% inhibitory dose （ICs0） of wild type MCF-7 and MCF-7/Taxol cells to Taxol was a- bout 0. 05 mg/L and 4. 2 mg/L respectively, and the resistance index was about 84. The resistance of MCF-7/Taxol cells to Taxol was reduced after treatment of As203 （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 As203, 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.

关 键 词：乳腺癌 耐药 紫杉醇 肿瘤干细胞 

分 类 号：R737.9[医药卫生—肿瘤]