Experimental study of the efficacy of L-lysine-a-oxidase Trichoderma CF. Aureoviride Rifai on models of xenografts of human tumors in athymic mice and evaluation of synergism with cisplatin or topoisomerase inhibitors

Abstract

The effectiveness of L-lysine-alpha oxidase Trichoderma cf. Aureoviride Rifai BKMF-4268D (LO) on models of subcutaneous xenografts of human tumors in athymic mice as well as the effectiveness of combination therapy with known antitumor drugs: cisplatin, irinotecan, etoposide on models of P388 lymphocytic leukemia, Lewis lung (LLC) and B16 melanoma was evaluated. The intraperitoneal injection of LO in a discrete regime at doses of 150-75-75-75-75 E/kg demonstrated inhibition of growth of all studied xenografts of human tumors in athymic mice. The combination of irinotecan+LO on the LLC model gave a significant summative therapeutic benefit with an increase in mouse life expectancy up to 35%. Cisplatin and LO realized a significant (p <0.05) therapeutic benefit against cisplatin according to an additive increase in the survival rate of mice with P388, UPJ = 208% vs. 128%; increased inhibition of growth of the primary node of melanoma B16, TPOmax = 87% vs. 58%. The addition of LO to etoposide did not lead to a significant improvement in the effect on the P388 model. The sensitivity to LO model of colon cancer and the presence of synergism with platinum and irinotecan drugs made LO a promising agent for the study in treatment for colon cancer