Скрининговое исследование эффективности и переносимости L-лизин-α-оксидазы из Trichoderma cf. aureoviride Rifai ВКМ F-4268D при пероральном введении на опухолевых моделях in vivo

Abstract

Introduction. Transformed cells are selectively vulnerable to a deficiency of certain amino acids. L-Lysine α-oxidase (LO) catalyzes the oxidative deamination of L-lysine, resulting in lysine depletion and hydrogen peroxide production. In preclinical models with intravenous and intraperitoneal administration LO shows a wide spectrum of antitumor activity. The purpose of this study was to determine the antitumor effect of orally administered to mice LO under tolerance control. Materials and methods. LO efficiency was studied on models Ca755 and SW620 when administered orally, evaluated using adequate criteria and the method of variation statistics and statistically significant differences at p≤0.05. Results. The antitumor activity and tolerance of LO from Trichoderma cf. aureoviride Rifai BKM F-4268D when administered orally was studied for the first time on murine and human tumor models. It was shown that LO in total doses of 6000-8000 U/kg (discrete mode of administration) reliably and significantly inhibits the growth of mouse breast adenocarcinoma Ca755, Tumor Growth Inhibition, TGImax=80-89% (p<0.05) (criterion of TGI≥50%). A smaller, but reliable effect was obtained on SW620 human colon cancer xenografts at a total dose of 6000 U/kg, T/C=75% (p<0.05) (criterion of T/C≤42%). By oral administration LO did not cause any side effects or death of mice from toxicity in the range of studied doses. Conclusion. This study makes it possible to consider LO promising for preclinical study with oral administration.