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

Tamanho da fonte: 
Botryosphaeran reduces tumor development and improves the metabolic profile of Walker-256 tumor-bearing obese rats
Danielli Geraldelli, Kamila Ortega Martins, Mariana Costa Ribeiro, Túlio Couto Medeiros, Matheus Fiori de Oliveira, Gabriela Alves de Oliveira, Robert Frans Huibert Dekker, Aneli de Melo Barbosa-Dekker, Pâmela Alegranci, Eveline Aparecida Isquierdo Fonseca de Queiroz

Última alteração: 09-10-19

Resumo


Abstract: Studies have been demonstrated that obesity is an important risk factor for tumor development, and chronic low-grade inflammation, oxidative stress, insulin resistance and hyperinsulinemia are the mechanisms related to carcinogenesis in obesity. Botryosphaeran, a (1→3)(1→6)-β-D-glucan, produced by the fungus Botryosphaeria rhodina, has been described as a potential drug for the treatment of obesity and cancer due to its antimutagenic, antiproliferative, pro-apoptotic, hypoglycaemic and hypocholesterolemic properties. Thus, the objective of this study was to evaluate the effects of botryosphaeran on Walker-256 tumor development in obesity and analyze the metabolic profile of these animals, under the hypothesis that botryosphaeran could reduce tumor development and improve its metabolic profile improving the insulin resistance. Study protocol was approved by the Ethics Committee under n°23108.973436/2018-54. Obesity was induced in male Wistar rats by ingestion of a high-fat high-sugar diet for 11 weeks. On 9th week, 1x107 Walker-256 tumor cells were inoculated subcutaneously into the upper right flank of the rats and treatment with botryosphaeran started (30mg/kg, via gavage, for 15 days). Thus, the rats were divided into two groups: Obese Tumor (OT) and Obese Tumor Botryosphaeran (OTB). At the 11th week, weight evolution, feed-intake, adipose and muscle tissues weights, glucose and lipid profiles, and hemogram were analyzed. Moreover, tumor development, percentage of rats that developed tumor, and cachexia syndrome were measured, as well as 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 reduced significantly the tumor development (OT=36.1±19.4g and OTB=16.8±8.0g#; #p<0.05) and the weight loss (OT= -55.5±31.2g and OTB= -7.8±13.1g#; #p<0.05), as well as decreased the cachexia index in 35%, demonstrating that this (1→3)(1→6)-β-D-glucan was effective to reduce tumor development and neoplastic cachexia. Furthermore, botryosphaeran significantly decreased mesenteric fat, and increased lean mass (soleus muscle) and insulin sensitivity. OT group presented hypochromic macrocytic anemia and botryosphaeran corrected this parameter. In the leukogram, all groups showed leukocytosis, neutrophilia and monocytosis, suggesting activation of the innate immune system. Moreover, OT animals presented lymphocytosis, suggesting an adaptive immune response. There was no change in the expression of the evaluated proteins. Botryosphaeran reduced tumor development and neoplastic cachexia in obese animals, mechanism associated with decreased fat accumulation and improved insulin sensitivity, confirming the potential role of botryosphaeran in the management of cancers.

Keywords: Obesity, Cancer, Botryosphaeran.


Palavras-chave


Obesity; Cancer; Botryosphaeran.