Molecular profile and cell cycle in mcf-7 cells resistant to cisplatin and doxorubicin

• Published in: Experimental Oncology
• Date: 2009
• Main Authors: Lukyanova, N.Yu., Rusetskya, N.V., Tregubova, N.A., Chekhun, V.F.
• Format: Article
• Language: English
• Published: Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України 2009
• Subjects: Original contributions
• Online Access: https://nasplib.isofts.kiev.ua/handle/123456789/135701
• Journal Title: Digital Library of Periodicals of National Academy of Sciences of Ukraine
• Cite this: Molecular profile and cell cycle in mcf-7 cells resistant to cisplatin and doxorubicin / N.Yu. Lukyanova, N.V. Rusetskya, N.A. Tregubova, V.F. Chekhun // Experimental Oncology. — 2009. — Т. 31, № 2. — С. 87–91. — Бібліогр.: 26 назв. — англ.

Aim: To compare ultrastructure, phenotypic profile and cell cycle progression ofMCF-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 ofBcl-2 expression) and intracellular glutathione detoxifying system are involved in the process of cisplatin resistance development
 inMCF-7 cells. Atthe 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 р21). Conclusion: The long-time culture of MCF-7 cells with cytostatic drugs results
 in the decreased cyclin D1, pRb, and Ki-67 expression and increased р21 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.