Sistema de Eventos Acadêmicos da UFMT, XI Mostra da Pós-Graduação

Tamanho da fonte: 
BOTRYOSPHAERAN DECREASES THE WALKER-256 TUMOR DEVELOPMENT AND THE CANCER CACHEXIA SYNDROME IN WISTAR RATS
Thais Pereira da Silva

Última alteração: 09-10-19

Resumo


Cancer is a multifactorial disease, characterized by an uncontrolled growth of cells. Botryosphaeran, a (1→3)(1→6)-β-D-glucan, produced by the fungus Botryosphaeria rhodina, has been described to present antimutagenic, hypoglycemic and hypocholesterolemic effects. Furthermore, a previous study demonstrated that botryosphaeran exhibited a direct antiproliferative and pro-apoptotic effect related to the activation of AMPK and FOXO3a in MCF-7 cells (in-vitro). So, we hypothesized that botryosphaeran can decrease the tumor development by a direct and indirect mechanism. Thus, the objective of this study was to analyze the botryosphaeran effects on tumor development in male Wistar rats and analyze the metabolic and hematologic profile of these animals. Study protocol was approved by the Ethics Committee under n°23108.973436/2018-54. Wistar rats (~400g) were divided into two groups: Control Tumor-CT and Control Tumor Botriosphaeran-CTB, and received standard ration and water ad libitum throughout the experimental period. On the first day of the experiment, 1x107 Walker-256 tumor cells were inoculated subcutaneously into the right flank of the rats, and concomitantly treatment with botryosphaeran (30mg/kg, via gavage, for 15 days) started. After the treatment, the animals were euthanized, and weight evolution, feed intake, adipose and muscle tissues weights, glucose and lipid profiles, and hemogram were analyzed. Moreover, tumor development and cachexia syndrome were measured, and the expression of proteins (Bax, Bcl-2, caspase-3, p27, p53 and FOXO3a) was determined by Western Blotting. The comparison between the groups was performed by Student's t-test and significant differences at p<0.05. Botryosphaeran significantly reduced tumor weight (CT=43.8±19.5g and CTB=12.5±9.0g#; #p<0.05) and the incidence of cachexia in the animals. Furthermore, the rats treated with botryosphaeran was not considered cachectic by the cachexia index (<10), demonstrating that this (1→3)(1→6)-β-D-glucan protected the animals from this condition. Botryosphaeran decreased the triglyceride and increased the HDL-cholesterol levels, and corrected the hypochromic macrocytic anemia, leukocytosis, lymphocytosis, and thrombocytopenia, presented by the CT group, improving the metabolic and hematologic conditions of these rats. CT and CTB groups presented neutrophilia and monocytosis, however, these parameters were significantly reduced in the CTB group. Finally, Bax (pro-apoptotic protein) expression was significantly higher in the CTB group demonstrating that botryosphaeran can be increasing the apoptosis of Walker-256 tumor cells by a direct or indirect mechanism. Botryosphaeran at a dose of 30 mg/kg/day was effective in reducing tumor development and cancer cachexia syndrome, increase the Bax expression, and improving the metabolic and hematologic profiles of the animals contributing to a better prognosis.


Palavras-chave


Cancer, Botryosphaeran, (1→3)(1→6)-β-D-glucan.