Efeitos inibitórios do Resveratrol na atividade migratória de células de melanoma cutâneo murinho e na formação de metástases pulmonares: avaliações in vitro e in vivo

Abstract

The metastasis is a pathological process characterized by the detachment of cells from the primary tumor into the bloodstream or lymphatic vessels, until reaches distant target organs, and is responsible for the low prognosis and increased morbidity associated with cancer. Melanoma is a skin cancer type with a great metastatic potential, due intrinsic characteristics of melanocytes. Besides that, melanoma shows resistance to existents treatments, and for this reason new therapeutic approaches have been sought. Resveratrol (Resv) is a compound naturally found in some foods, such as grapes, and has a wide range of beneficial effects on human health, acting in several signaling pathways. The aim of this study was to investigate the effect of Resv in the migration of B16F10 murine cutaneous melanoma cells in vitro, and in the formation of lung metastases in a model of syngeneic metastatic melanoma. B16F10 murine cutaneous melanoma cells were used in in vivo and in vitro assays. To the migration assay, 4 × 105 B16F10 cells were seeded, and after 24 hours of incubation they were treated with Resv at concentrations 25, 50, and 100 μg / mL and a wound was made in the plate. The cells were incubated for further 48 hours and were analysed. To establish the syngenic model of lungs metastasis in vivo, 5 × 105 B16F10 cells were inoculated intravenously through the tail vein of C57BL/6 mice. The mice received Resv 400 mg/Kg or PBS (control group), daily by gavage, for 23 days before inoculation and for further 20 days after inoculation. The mice were euthanized, the lungs were removed and histopathological and histomorphometric analyzes were performed. Resv significantly (p < 0,05) decreased the migratory activity of B16F10 cells in vitro,in a dose-dependent manner. In the lung metastasis model, the Resv400 administration reduced the development of lung metastases in C57BL/6 mice. The lungs of mice treated with Resv400 showed less amount and area of metastatic nodules, when compared with control ones, with a high size effect. Resv has an anti-migratory activity on B16F10 cells and showed an anti- metastatic potential on the lungs of C57BL/6 mice.