Nikulina V. Сharacteristics of influence the compounds of synthetic and natural origin on cellular targets in angiogenesis

Nowadays, agents which, in addition to specific effect on cellular and molecular targets of tumor growth and ischemia, posses the ability to inhibit or activate angiogenesis, are attractive for therapeutic angiogenesis-dependent correction of pathological states, which has vascular-dependent outcome. The role of non-specific modifiers of angiogenesis in regulation of cellular and systemic responses was revealed using the model of tumor growth in vivo and cultured malignant and endothelial cells in vitro. Antitumor and antimetastatic efficacy of biopolymer from cell wall of gram-positive microorganisms Staphylococcus aureus - techoic acid in joint application of bimetallic compound of copper and cadmium was shown on transplantable Lewis lung carcinoma model. Such effect was linked with enhancement of tumor-infiltrating lymphocytes level. Reversal of substrate-independent growth of tumor cells after aforementioned application was observed on multicellular spheroids model. Angiogenesis-mediated effect of this biopolymer was manifested as modification of endothelial cell cycle parameters and change in duration of adaptive period in synchronized culture. It was demonstrated that G0/G1 subpopulation of cultured tumor cells was on 25,5% and 12% increased in comparison with control and Herceptin respectively in response to joint influence of epithelial cells mitogen EGF, drug Herceptin and humanized monoclonal antibody to EGF receptor II type. It was accompanied by decreasing of MCF-7 cell migration area on substrate by 9 times compared with the control and 1,7 times compared to Herceptin. These results may indirectly indicate inhibition of tumor cell invasion processes in vascular network. Obtained data indicate that new compounds (derivatives of 2- (2-aminothiazol-4-yl)-2-hydroxyiminoacetic acid) analogue of hypoxia-inducible factor inhibitors can stimulate or inhibit the proliferation of endothelial cells and commit cytotoxic and proapoptotic effect on tumor cells depending on transisomerism. Positive corrective effect of trofinotropin mitokorrektin drug, which is used for anti-ischemia and anti-stroke treatment, on angiogenesis was shown in in vitro studies. It was confirmed by its involvement in proliferation and differentiation of endothelial cells.