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Information × Registration Number 0220U000612, 0116U000039 , R & D reports Title Development of cell test system to evaluate the efficacy and mechanisms of action of antineoplastic drugs. popup.stage_title Head Sydorenko Myhail V., Registration Date 06-07-2020 Organization "Department of Biotechnical Problems in Diagnostic of Institute of Problems of Cryobiology and Cryomedicine National Academy of Sciences of Ukraine" popup.description2 Abstract. Research report: p. 41, fig. - 11 tablets - 2, link sources - 53. Object of research: tumor spheroids of the MCF-7 line, Doxorubicin, Methotrexate, Cisplatin, Salinomycin. The work involved cytological, immunological, biochemical and statistical methods of analysis. The aim of the study was to compare the reactivity of monolayer and spheroid cultures under conditions of modification of microenvironment factors. Determination of proliferative, morphological, kinetic characteristics of spheroids and monolayer culture under incubation conditions with antitumor drugs and Salinomycin.The objectives of the study were to determine the sensitivity of tumor cells in a monolayer culture to classical antitumor drugs compared to Salinomycin. Determination of the effect of antitumor drugs and Salinomycin on the receptor profile of breast cancer cells and on the pool of stem tumor cells, as well as on the ability of tumor cells to form colonies.As a result of studies, it was found that tumor cells in 2D culture are the least sensitive to the effects of methotrexate (IC 50 - 67.22). The cytotoxic effects of Doxorubicin and Salinomycin were the same. IC 50 Doxorubicin - 14.93, IC 50 Salinomycin - 14.5. Cisplatin had the greatest cytotoxic effect on MCF-7 cells in a monolayer culture, IC 50 - 2.52. At the same time, under the influence of salinomycin at a concentration of 30.0 ?g / ml, the expression of CDK markers CD133 (1.4 times) and CD44 (1.3 times) was slightly reduced, and bmi-1 expression remained at the control level. At the same time, the expression of cytokeratins statistically significantly increased by 2.3 times, and R-EGF decreased by 3.7 times. Incubation of tumor cells in the presence of cisplatin (1.0 ?g / ml) statistically significantly stimulated a decrease in the expression of SEC markers: CD44 (2.3 times), CD133 (6.5 times), bmi-1 (1.2 times) and an increase in the expression of cytokeratins 8 and 14 by 1.2 times, and P-EGF by 1.3 times, compared with the control. The cultivation of MCF-7 cells in the presence of methotrexate at a concentration of 10.0 ?g/ml led to a significant increase in the number of cells expressing stem tumor cell markers compared to control samples: CD133 - 1.3 times, CD44 - 2 times, bmi - 1.2 times. At the same time, the percentage of MCF-7 cells expressing cytokeratins 8 and 14 and R-EGF decreased (by 4.3 and 2.9 times, respectively). In the presence of doxorubicin 10.0 ?g/ml, as well as during incubation with metatrexate, the expression of cytokeratins 8 and 14 (1.7 times) and R-EGF (1.5 times) was statistically significantly reduced. At the same time, the expression of CD44 (2.2 times), CD133 (1.5 times), bmi-1 (1.4 times) increased compared with the control. Salinomycin (30.0 ?g / ml) and Cisplatin (1.0 ?g / ml) had the greatest impact on the ability of MCF-7 cells to form colonies. Incubation with these drugs led to a decrease in the number of colonies by 65% ??and 60%, respectively, compared with the control. The clonogenic ability of MCF-7 after a short incubation with Doxorubicin was reduced by 50% compared with the control. Methotrexate had the least effect on the ability of tumor cells to form colonies in the adhesive fraction among the studied drugs - the decrease in the ability of tumor cells to form colonies was 40% compared with the control. Thus, it was suggested that Cisplatin and Salinomycin have a cytotoxic effect on the population of MCF-7 stem tumor cells in a monolayer culture and cause a decrease in the ability of cells to form colonies. Metatrexate and Doxorubicin also have a cytotoxic effect on tumor cells, but this does not lead to a decrease in the stem tumor pool and a decrease in the ability of cells to form colonies. Scientific and practical significance. The data obtained illustrate the heterogeneity of the tumor cell population and the ability to change the phenotype depending on the microenvironment conditions. A new antibiotic, Salinomycin, was tested, comparing its effect on tumor cells with the effect of classical antitumor drugs. As a result of studies, it was revealed which pools of tumor cells are sensitive to each of the studied drugs, which will allow developing new treatment regimens for cancer patients. Further research will be continued on the model of multicellular tumor spheroids to determine the effect of drugs on the pool of stem tumor cells. Key words: MCF-7 spheroids, Doxorubicin, Methotrexate, Cisplatin, Salinomycin Product Description popup.authors Гергелюк Т.С. Железна М.В. Лебедєва Т.М. Перепелиціна Олена Михайлівна Просяник Л.Б. Сидоренко Михайло Васильвич Фіда В.В. popup.nrat_date 2020-10-01 Close