O.O. Ryabaya, N.M. Peretolchina, V.A. Golubeva, E.K. Fetisova, I.I. Galkin, M.V. Kiselevskiy, F.V. Donenko, E.V. Stepanova

Multidrug resistance (MDR) of tumors to chemotherapy is studied for a long time, but the challenge of overcoming it is still not resolved. This phenomenon brings together the cases in which tumor cells are insensitive or become insensitive to the effects of anticancer drugs, which differ structurally and functionally [6, 7]. MDR is a major problem in the treatment of cancer, leading to a decrease in survival and a high socio-economic damage. Currently described the various mechanisms involved in the formation of MDR: activation of transmembrane transporters, efflux pumps various chemical compounds from the cells, the activation of enzymes glutathione detoxification system, changes in genes and proteins that control apoptosis [6]. One of the major and most studied mechanisms of MDR is the overexpression of P-glycoprotein (Pgp170, MDR1) [7]. In some cases the resistance of tumor cells to anticancer drugs, including doxorubicin, correlates well with the low efficiency of radiation therapy [1, 8]. Since the basis of the different kinds of exposures is the induction of oxidative stress, the latter may be due to the fact that the development of resistance induced by the prooxidant effects of chemotherapeutic agents such as doxorubicin, there is an increased expression of genes encoding key antioxidant enzymes - catalase, superoxide dismutase, glutathione peroxidase [5]. The use of cell lines that have MDR, as models to assess the efficacy of new anticancer drugs and combination regimens of chemotherapy and radiotherapy will identify new approaches to overcome MDR. In Russian Cancer Research Center a strain of P388 leukemia with doxorubicin-induced resistantance P388/DOX was obtained. To do this, increasing concentrations of doxorubicin (0,5 mg/kg to 10 mg/kg) were administered to mice line DBA/2, inoculated with the original strain of leukemia cells P388, twice a week for a year. It was shown that P388/DOX leukemia cells characterized as resistant to most cytotoxic drugs of natural origin (mitomycin C, vincristine, and others) as compared to the original strain of P388 [9]. The aim of this research was to assess the radiosensitivity of P388 leukemia cells with induced resistance to doxorubicin, as well as the functional activity of P-glycoprotein in them.