Lukyanova N Yu, Rusetskya N V, Tregubova N A, Chekhun V F
R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology NAS of Ukraine, Kyiv 03022, Ukraine.
Exp Oncol. 2009 Jun;31(2):87-91.
To compare ultrastructure, phenotypic profile and cell cycle progression of MCF-7 human breast cancer cells and MCF7 sublines resistant to cisplatin (MCF-7/DDP) and doxorubicin (MCF-7/DOX).
MTT-test, immunocytochemistry, flow cytometry, electron microscopy.
The development of drug resistance to cisplatin and doxorubicin in MCF-7 cells upon the culturing of the initial cells with the raising concentrations of cytostatics was accompanied by the increase in cells adhesion, the increasing differentiation grade and the loss of steroid hormone receptors. Besides, it was shown that antiapoptotic mechanisms (decrease of Bcl-2 expression) and intracellular glutathione detoxifying system are involved in the process of cisplatin resistance development in MCF-7 cells. At the same time, P-glycoprotein overexpression in cells resistant to doxorubicin suggests MDR-dependent mechanism. Both doxorubicin- and cisplatin-resistant cells are characterized by the changes in the expression of several cell cycle regulators -- Ki-67, cyclin D1, pRb and p21).
The long-time culture of MCF-7 cells with cytostatic drugs results in the decreased cyclin D1, pRb, and Ki-67 expression and increased p21 expression with the increasing differentiation grade of the resistant cells. The underlying mechanisms of resistance to cisplatin and doxorubicin in MCF-7 cells may be different.
比较MCF-7人乳腺癌细胞以及对顺铂（MCF-7/DDP）和阿霉素（MCF-7/DOX）耐药的MCF7亚系的超微结构、表型特征和细胞周期进程。
MTT试验、免疫细胞化学、流式细胞术、电子显微镜检查。
用逐渐增加浓度的细胞抑制剂培养初始细胞后，MCF-7细胞对顺铂和阿霉素产生耐药性，同时细胞黏附增加、分化程度提高以及类固醇激素受体丧失。此外，研究表明抗凋亡机制（Bcl-2表达降低）和细胞内谷胱甘肽解毒系统参与了MCF-7细胞顺铂耐药性的形成过程。同时，对阿霉素耐药的细胞中P-糖蛋白过度表达提示存在多药耐药依赖性机制。对阿霉素和顺铂耐药的细胞均表现出几种细胞周期调节因子（Ki-67、细胞周期蛋白D1、pRb和p21）表达的变化。
用细胞抑制剂长期培养MCF-7细胞会导致细胞周期蛋白D1、pRb和Ki-67表达降低，p21表达增加，耐药细胞的分化程度提高。MCF-7细胞对顺铂和阿霉素耐药的潜在机制可能不同。
