Molecular profile and cell cycle in MCF-7 cells resistant to cisplatin and doxorubicin.
OBJECTIVE
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).


METHODS
MTT-test, immunocytochemistry, flow cytometry, electron microscopy.


RESULTS
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).


CONCLUSIONS
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.
Lukyanova
N Yu
NY
R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology NAS of Ukraine, Kyiv 03022, Ukraine. oncom@onconet.kiev.ua
Rusetskya
N V
NV
Tregubova
N A
NA
Chekhun
V F
VF
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000235:genetics* / Q000648:ultrastructure; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D046529:Microscopy, Electron, Transmission
D000970:Antineoplastic Agents; D004317:Doxorubicin; D002945:Cisplatin