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Manifestation of Key Molecular Genetic Markers in Pharmacocorrection of Endogenous Iron Metabolism in MCF-7 and MCF-7/DDP Human Breast Cancer Cells

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CellBio 2013年第4期2卷 217-227页

作者： Vasyl’ Chekhun Natalia Lukianova dmytro demash Tetiana Borikun Svyatoslav Chekhun Yulia Shvets Department of Mechanisms of Antitumor Therapy R.E. Kavetsky Institute of Experimental Pathology Oncology and Radiobiology NAS of Ukraine Kyiv Ukraine

Effects of the nanocomposite and its components (magnetic fluid, cisplatin) on the level of endogenous iron exchange and the key links of genetic and epigenetic regulation of apoptotic program of sensitive and resistant MCF-7 cells were examined. We showed genetic and epigenetic mechanisms of action of nanocomposite of magnetic fluid and cisplatin. Nanocomposite caused elevation of number of cells in apoptosis in sensitive and especially resistant MCF-7 cells compared to cisplatin alone. It was proved that impact of nanocomposite on MCF-7/S and MCF-7/DDP cells caused more significant changes in expression of apoptosis regulators p53, Bcl-2 and Bax. We also suggested that changes in endogenous iron homeostasis and activation of free radical processes caused significant impact on apoptosis. Those changes included changes in methylation and expression of transferrin, its receptors, ferritin heavy and light chains (predominantly in resistant cell line), which caused activation of free radical synthesis and development of oxidative stress. We also showed that nanocomposite impact resulted into significant changes in expression of miRNA-34a and miRNA-200b, which regulated apoptosis, cell adhesion, invasion and activity of ferritin heavy chains gene. Thus, use of nanocomposite containing cisplatin and ferromagnetic as exogenous source of Fe ions caused changes of endogenous iron levels in sensitive and resistant cells allowing to increase specific activity of cytostatics and overcome factors, which promoted MDR development. Pharmacocorrection of endogenous iron metabolism allowed increasing antitumor activity of cisplatin and overcoming drug resistance.

关键词： Nanocomposite Iron Metabolism Apoptosis ROS Drug Resistance Breast Cancer Cells

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Evaluation of Biological Effects of Nanosystems of Directed Transport in Experiments <i>in Vivo</i>and Their Application Possibilities in Anti-Tumor Therapy

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Advances in Nanoparticles 2013年第2期2卷 145-153页

作者： Vasyl F. Chekhun Lesia A. Naleskina Liudmila Z. Polishchuk Igor M. Todor dmytro V. demash Natalia Yu. Lukianova Department of Mechanisms of Anti-Tumor Therapy RE Kavetsky Institute of Experimental Pathology Oncology and Radiobiology of National Academy of Sciences of Ukraine Kyiv Ukraine

The aim of the investigations was to evaluate benefits of the directed transport system - a nanocomposite, based on cisplatin and magnetite combined with local action of constant magnetic field on the tumor, in experiments in vivo in animals with transplantable Guerin carcinoma. Animals were divided into 5 groups according to the type of agent. We showed that nanocomposite in combination with static magnetic field exercises more prominent anti-tumor activity than cisplatin alone. It should be noted that regardless of the therapeutic agent, in Guerin carcinoma we observed

关键词： Oncology Nanocomposite Static Magnetic Field Cisplatin Anti-Tumor Activity Guerin Carcinoma

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