Ultrastructural changes in tumor cells treated with liposomal forms of anticancer drugs.

AIM: To determine the main ultrastructural changes in MCF-7 sublines sensitive and resistant to cytotoxic action of anticancer drugs, resulting from the treatment with conventional and liposomal forms of cisplatin and doxorubicin. METHODS: Electron microscopy, light microscopy, MTT-test. RESULTS: It has been shown that the phenomenon of drug resistance is associated with complication of ultrastructural organization of cells and more high differentiation by the main cytomorphologic characteristics which promote their resistance to cytotoxic action of anticancer preparations. Cytoarchitectonics of all resistant cells possesses common patterns and doesn't depend on the particular drugs toward which the resistance has been developed. It has been shown that the cells of the parental form MCF-7 line are more sensitive to cytotoxic action of doxorubicin than to cisplatin. Liposomal forms of anticancer drugs used at the same concentrations that the conventional ones, especially that of doxorubicin, caused more expressed alterations in ultrastructural organization of cells of all studied sublines with dominance of apoptotic processes. CONCLUSION: Evaluating an effect of equal concentrations of cisplatin and doxorubicin in conventional and liposomal forms, one may conclude on higher cytotoxic action of doxorubicin vs. cisplatin that is expressed in a wider spectrum of ultrastructural changes of cell architectonics in different sublines of MCF-7 cells and higher rate of apoptosis.

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

AIM: 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). 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 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.