Efeitos do resveratrol na progressão do modelo tumoral murino singênico de melanoma cutâneo em camundongos C57BL6

Abstract

Cancer is a pathological process marked by autonomy of cell proliferation, acquisition of undifferentiated phenotypes, ability to invade local and distant tissues (metastases) and resistance to the activation of mechanisms of cell death. Cutaneous melanoma (CM) represents a cancer originated in skin melanocytes, being very aggressive due to its early metastatic capacity. Clinically, CM exhibits few therapeutic alternatives, especially in cases where the disease is in advanced stages, resulting in high rates of morbidity and mortality. The polyphenols found in the diet can affect and modulate numerous processes and several biochemical pathways included in carcinogenesis, with Resveratrol (Resv) being a natural phytoalexin with great potential and significant perspectives. The present study evaluated the effects of oral administration of Resv on the progression of the cutaneous murine tumor model of cutaneous melanoma (SMCMTM) and on cancer-related survival in C57BL/6 mice. The design of the in vivo study was approved by the Ethics Committee on Experimentation and Animal Welfare (CEEBEA/Unimontes/N°:131/2017). The research comprised two distinct stages, in the first, it evaluated the tumor progression and in the second, the survival of the mice. In order to establish the SMCMTM, female C57BL/6 mice (n=60) were inoculated in the dorsal subcutaneous region with 5×105 of the murine MC cell line, B16-F10. For analysis of tumor progression, the animals were divided into three study groups: Control; Resv200 and Resv400. After the appearance of a clinically palpable tumor, the mice were monitored daily to measure the tumor volume with the aid of a digital caliper (mm3). In order to strengthen these data, it was also used to evaluate the tumor volume (mL), using a Doppler ultrasound device on days 5, 8 and 11 of the experimental period. The animals were treated for a period of 11 days, and euthanasia occurred on the twelfth day of follow-up. For the analysis of cancer-related survival, the animals were also submitted to SMCMTM, the division of the groups being identical to that used to assess the effect on tumor progression. The mice were treated and monitored for the daily death record, until the last death of each group occurred. The results showed that animals treated with Resv 200mg/Kg and 400mg/Kg exhibited a significant reduction in tumor volume (p <0.001) and weight (g) (p <0.05 and p <0.01 respectively). In addition, there was a benefit of Resv in cancer-related survival of treated animals compared to the control group without treatment (p = 0.038 and p = 0.040, respectively). Therefore, the results of this study allowed us to conclude that the administration of Resv reduced the tumor volume and weight, occurring in the increased survival rates of the C56BL/6 animals that were induced to SMCMTM. In addition, our data support the use of the substance Resv as an adjunct therapy in cancer management.