Establishment of an orthotopic tumor model in the mammary gland of BALB/C NUDE mice using human breast cancer MCF-7 cells and their VDAC-deficient derivatives

Purpose to study the tumor-forming activity of wild-type mcF-7 cells carrying a full set of porins (Vdac1, Vdac2, Vdac3), as well as their genetically modified cells, from which one of the isoforms was removed (mcF-7 Vdac1 Ko, mcF-7 Vdac2 Ko, mcF -7 Vdac3 Ko). material and methods. the study was aimed at establishing of an animal model of orthotopic tumors in the mammary gland of immunodeficient BalB/c nude mice by implanting a suspension of human breast cancer cells (mcF-7) and derivatives of these cells generated by targeted knockout of one of the selected mitochondrial porin isoforms (Vdac1, Vdac2 or Vdac3). suspensions of either wild-type mcF-7 cell lines containing all three porin isoforms (Vdac1, Vdac2 and Vdac3) or their Vdac-deficient derivatives (mcF-7 Vdac1 Ko, mcF-7 Vdac2 Ko and mcF-7 Vdac3 Ko) were injected into mammary fat pads of BalB/c nude mice at a dose of 4x106 cells per injec-tion. a pathomorphological analysis of the place of implantation of tumor cells, the tumor itself, as well as the organs of the abdominal and thoracic cavity was carried out. Results. the study shows the feasibility of successful creation of orthotopic tumors in the adipose tissue of immunodeficient BalB/c nude mice with mcF-7 human breast cancer epithelial cells containing a complete set of mitochondrial porin isoforms and their Vdac-deficient derivatives. the tumor-forming activity of the implanted cells was shown to correlate with their cytotoxic effect on the internal organs of animals. pathological analysis showed that all implanted cell cultures, such as mcF-7 Wt, mcF-7 Vdac2 Ko and mcF-7 Vdac3 Ko, except for mcF-7 Vdac1 Ko cells, which did not form tumors, caused pathological changes in the lungs, liver and spleen, as well as the presence of other tumor-like lesions. conclusion. the data obtained will be used to optimize the injection volume and cell number, as well as to refine the dynamics of tumor growth, suitable for studying the effect of anticancer drugs on tumors formed by human breast cancer cells (mcF-7) and its genetically modified Vdac-deficient derivatives.