Proliferative Activity of Ehrlich Carcinoma Cells After Use of Nanocomplexes

Investigation of functional state of tumor cells, peculiarities of the pathology development, and sensitivity of tumor cells to the therapeutic agents is an urgent task of modern oncology. It has previously been shown that nanocomplexes (NCs) containing nanoparticles of rare earth orthovanadates GdYEuVO4 and cholesterol are capable of inhibiting the functional activity of Ehrlich ascites carcinoma (EAC) cells. One of the criteria for assessing the change in proliferative activity of EAC cells influenced by nanocomplexes is the rate of Ki-67 antigen expression. It is assumed when influenced by NCs the activity of pluripotency genes in tumor cells may be modulated. The EAC was found to be an aggressive tumor, as evidenced by the number of Ki-67+—cells in total EAC population and the isolated from it by magnetic sorting CD44+—fraction at the level of 95.6 ± 7.4% and 99.04 ± 8.5%, respectively. The cells obtained from the CD44+—fraction had a significantly higher average fluorescence intensity of the Ki-67 marker compared with total EAC population-derived cells. The ability of NCs to inhibit the proliferative activity of the CD44+—fraction in a bigger extent than the cells of total EAC population, judging by the maximum reduction in the number of Ki-67+ cells, was established. This stipulated the inhibition of tumor growth by 88.95 ± 5.78% and extended the lifespan of tumor-bearing animals by a third. Under the influence of NCs in the peritoneal cavity of mice, there was formed an ascites with reduced expression of nanog, oct4, sox2 pluripotency genes, and the corresponding transcription factors in cells of total EAC population and CD44+ fraction. Under the effect of NCs, the maximum inhibition of nanog gene expression and the minimum one of the sox2 gene have been shown. The results indicate the NCs are capable to inhibit the proliferative activity of EAC and the antitumor effect of NCs is realized by synergistical reducing of expression rate of pluripotency genes (nanog, oct4, sox2) and the corresponding transcription factors (nanog and oct3/4).