摘要
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.
出处
《细胞生物学杂志》
CSCD
2006年第4期591-595,共5页
Chinese Journal of Cell Biology