In-vivo evaluation of DT386-BR2, a promising anticancer fusion protein, in mice model

Abstract

Background: Cancer is one of the greatest health-related problems and due to increasing drug resistance and severe side effects of chemotherapeutic agents, production of targeted anticancer agents with lower side effects is under consideration. Previously, we produced a fusion protein consisted of catalytic and translocation domains of diphtheria toxin (DT386) fused to BR2, a cancer specific cell penetrating peptide. First steps of this study showed selective antiproliferative effects of DT386-BR2 on cancer cells but not on normal cell lines. The aim of the present study was evaluation of its in-vivo non-specific toxicity in healthy mice. Methods: The fusion protein was produced and purified through recombinant DNA technology. Intraperitoneal injections with various concentrations of DT386-BR2 were done in healthy mice for five consecutive days and they observed for 14 days after the last injection inspecting their food consumption, body weight, body temperature, and finally being dead or alive. Negative controls were injected with normal saline solution. Findings: There was not any significant effect on temperature, body weight, and viability of mice received various concentrations of DT386-BR2 (P < 0.05), and increasing the protein concentration did not show any adverse effects on mice. Conclusion: DT386-BR2 can be used for further pre-clinical studies to determine its pharmacokinetics/pharmacodynamics profiles and evaluation of its anticancer efficacy in suitable xenograft animal models. © 2017, Isfahan University of Medical Sciences(IUMS). All rights reserved.