人乳腺癌多药耐药细胞系MCF-7/MDR^a的建立及其生物学特性的初步研究

Establishment of Multidrug-resistant Breast Cancer Cell Line MCF-7/MDR^a and Its Preliminary Analysis on the Biological Properties

实验以MCF-7细胞株为亲本细胞,采用阿霉素(ADM)低浓度持续加量诱导法建立了多药耐药的人乳腺癌细胞系MCF-7/MDRa,并对其耐药谱、动力学周期分布、表型变化、药物的蓄积量等生物学特性进行了初步分析评价。结果表明,MCF-7/MDRa细胞较亲本细胞的ADM半数致死浓度(IC50)高500倍,撤药培养150天后耐药指数仍维持在200倍以上,并对多种化疗药物产生交叉耐药性;耐药细胞分化程度低于同步传代的MCF-7细胞,细胞倍增时间与亲本细胞接近,S期细胞显著增加,G1期细胞减少;随着撤药时间的延长,细胞的增殖速度加快;耐药细胞P-gP、LRP和GSTπ的表达水平较亲本细胞有显著增加,ER阳性表达丢失;在稳定生长的撤药培养6天的细胞中仍有ADM蓄积。建立的MCF-7/MDRa模型具有多药耐药细胞的基本生物学特性,可用于肿瘤多药耐药机制的研究。

In this paper a line of breast cancer cell named MCF-7/MDR^a with multidrug-resistance was established, and its elementary biological properties including drug-resistance, cell cycle dynamics, exterior transformation, and intracellular drug accumulation and so on, were analyzed. Results showed that MCF-7/MDR^a was of good resistance to several chemotherapeutants for tumor. The IC50 of MCF-7/MDR^a to ADM was 500 times higher than that of nature MCF-7, and its IC50 to other chemotherapyagents was 6-75 times higher too. However, the drug resistant index of the cells could keep on over 200 times higher after culturing MCF-7/MDR^a in the medium （without ADM） for 150 days. The multiplication time of MCF-7/MDR^a was similar to that of their nature cells, but the most cells concentrated in S-phase and the least cells in G：phase of the cell cycle. The multiplication time could be accelerated in evidence with culturing the cells in the medium （without ADM）. The expression levels of P-gp, LRP and GSTπ on the cells increased significantly except for ER. The level of intracellular ADM concentration of the cells remained high quantity even after 6-day culture in the medium （without ADM）. The results indicated that the multidrug-resistant cell species （MCF-7/MDR^a） established in this study was of good biological characteristics, multidrug-resistance especially, which would be helpful to research on MDR mechanism of cancer cells.