ИСТИНА

TiO2 are widely used in industry and in the production of cosmetics and medicines cosmetics and medicines production?. TiO2 can accumulate in the different tissues, without pronounced toxic effects at low concentrations. In recent years, to achieve tumor-specific delivery of anticancer agents, TiO2 nanoparticles (NP) has been used in chemo/photodynamic therapy, which may cause local increase of the TiO2 concentration in tumors. The TiO2 NP may influence affect? various processes in tumors. One of such process is entosis. Entosis is a type of cell cannibalism during which one tumor cell invades the other tumor cell. It is shown that invasion occurs with participation of acto-myosin complex and formation of adhesive junctions between outer and inner cells. The fate of inner cell can be different: it can leave the entotic vacuole, divide within it, or be subjected to lysosome-mediated degradation (which suppresses neoplastic transformation). Entosis is now shown to perturb cytokinesis of outer cell and induce the formation of aneuploid cells, which leads to acceleration of neoplastic transformation.The aim of this work was to study the effect of TiO2 NP(anatase <25nmand rutil/anatase <75nm; 1, 10 and 100 µg/ml, 72 hours)on the entosis in the human breast adenocarcinoma cell line (MCF7).Exposure with TiO2 NP inhibited entosis, increased apoptosis and decreased mitotic activity. These effects were dose-dependent. Elemental analysis using electron microscopy showed presence TiO2 NP in the cell vacuoles and near plasma membrane in the extracellular space.TiO2 NP in a concentration of 10 µg/ml significantly disrupted adhesive junctions (beta- catenin immunostaining, F-actin staining) in entotic cells and in cell culture in general. Treatment with TiO2 NP increased lysosomal activity of mononuclear cells, but inhibited this process in the the entotic vacuoles. The anatase NP induced p53 translocation into the nucleus that assumed activation of cell cycle block and prevention the entry of the outer cell in mitosis. Thus, the obtained data showed that the TiO2 NP inhibited entosis in MCF-7 cells by means of disrupting the adhesive junction formation and preventing cell invasion. So, on the one hand, TiO2 NP can inhibite tumor transformation caused by entosis. However, on the other hand, failure of adhesive contacts can facilitate tumor metastasis.