Search academic texts

Information × Registration Number 0223U005002, 0120U104156 , R & D reports Title Differential control of regulatory networks involved in the maintaining of epithelial-mesenchymal plasticity of breast adenocarcinoma cells popup.stage_title Head Drobot Liudmyla B., Доктор біологічних наук Registration Date 12-12-2023 Organization Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine popup.description2 It was established that MCF-7 and 4T1 RukUp adenocarcinoma cells acquire morphological, biological and biochemical features of cancer stem cells. It was also shown that according to morphological features 4T1 RukUp cells acquire an amoeboid phenotype, which correlates with their highly aggressive behavior. A number of key components of cell signaling networks inhibitors were screened for their effect on the aggressiveness of 4T1 cells. It was demonstrated that 1) the Src kinase inhibitor (PP2) had the greatest ability to suppress the migratory and the metabolic activity of 4T1 RukUp cells as compared to Mock cells$ 2) apocynin, an inhibitor of NADPH-oxidase complex assembly, effectively inhibited the invasive potential of MCF-7 RukUp cells; 3) the LDHA inhibitor, NHI-2, decreased the viability and migration rate of all sublines of 4T1 cells, while RukUp cells were most sensitive to NHI-2; 4) histone deacetylase 1 inhibitor, VPA, restored the coupling between oxidative phosphorylation and glycolysis in 4T1 RukUp cells, indicating an attenuation of the aggressive phenotype of these cells. Features of metastasis of 4T1 RukUp cells under the influence of Src kinase PP2 inhibitor, differentiation inducer, vitamin D3 hormonal form and histone deacetylase 1 inhibitor, VPA, were analyzed by using the Balb/c syngeneic mouse model. Histological analysis of tissue sections (hematoxylin and eosin) showed that metastases developing in the internal organs of mice (lungs, heart, liver) of the control group were completely suppressed when PP2 and VPA were administered to mice, and when 1,25-OH D3 was administered to these mice conditions were accompanied by the development of metastases in only 20% of animals and the formation of perivascular foci of infiltrated inflammatory cells. The results of studies of the effects of the used inhibitors indicate their effect directly on tumor cells by blocking their extravasation into target organs. Product Description popup.authors Bekala Mark Gerashchenko Olga Leonydivna Horak Iryna Iryna R. Hrabovskyi Oleksii Olehovych Drobot Liudmyla B. Korshun Ruslan Sergiyovych Latyshko Nely Nely V. Mazanova Anna Oleksandrivna Stohnii Yevhen M. Yatsenko Tetiana Andriivna popup.nrat_date 2023-12-12 Close