RESUMO
Female FVB/N HER-2/neu transgenic mice from the age of 2 months were subcutaneously injected with saline, the peptide Epitalon(R) (Ala-Glu-Asp-Gly) or with the peptide Vilon(R) (Lys-Glu) in a single dose of 1 microg/mouse for 5 consecutive days every month. Epitalon treatment reduced the cumulative number and the maximum size of tumors (p < 0.05). Furthermore, the number of mice bearing 1 mammary tumor was increased, whereas the number of mice bearing 2 or more mammary tumors was reduced in Epitalon-treated in comparison to saline-treated animals (p < 0.05). The size but not the number of lung metastases was reduced in Epitalon-treated compared to saline-treated mice (p < 0.05). The treatment with Vilon produced significant negative effects when compared to the control group, with an increased incidence of mammary cancer development (p < 0.05), a shorter mean latent period of tumors (p < 0.05) and an increased cumulative number of tumors (p < 0.05). A 3.7-fold reduction in the expression of HER-2/neu mRNA was found in mammary tumors from HER-2/neu transgenic mice treated with Epitalon compared to control animals. The expression of mRNA for HER-2/neu was also partially reduced in Vilon-treated mice, but it remained significantly higher in Vilon- than in Epitalon-treated animals (1.9-fold increase). The data demonstrate the inhibitory effect of Epitalon in the development of spontaneous mammary tumors in HER-2/neu mice, suggesting that a downregulation of HER-2/neu gene expression in mammary adenocarcinoma may be responsible, at least in part, for the antitumor effect of the peptide.
Assuntos
Neoplasias Mamárias Animais/tratamento farmacológico , Neoplasias Mamárias Animais/patologia , Oligopeptídeos/uso terapêutico , Receptor ErbB-2/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Dipeptídeos/farmacologia , Comportamento Alimentar/efeitos dos fármacos , Feminino , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Camundongos , Camundongos Transgênicos , Oligopeptídeos/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptor ErbB-2/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de TempoRESUMO
In the present paper, we investigated whether the phenotype, the antigen-presenting capacity, and the migration of antigen-presenting cells (APCs), are affected by the aging process. APCs were obtained incubating peritoneal monocyte-macrophage cells with granulocyte-macrophage colony-stimulating factor (GM-CSF) (immature APCs) or GM-CSF and IFNgamma (mature APCs). Phenotypically, after 8 days incubation, APCs cultures were composed of CD11c and Mac-3 cells, with a similar representation, both in young and old mice. The absolute number and the expression of MHC I and II, CD80, and CD86 both on immature and mature APCs were not significantly different in young and old mice. APCs from old mice induced similar lymphocyte proliferative responses but lower lymphocyte cytotoxicity and a reduced number of CD8(+) T cells producing IFNgamma in comparison with APCs from young animals. Lymphocyte responses were antigen-specific, since TS/A pulsed APCs induced lymphocyte cytotoxicity against TS/A but not against syngeneic TUBO tumor cells. The low expression of the mRNA for the migratory CCR7 chemokine receptor present in immature APCs from old mice was greatly increased in mature APCs up to the levels found in APCs from young animals. The in vivo migration of APCs was higher in old than in young mice. These results demonstrate that some alterations in APCs function are present in aging, suggesting that an increased migratory capacity of old APCs may be required to balance their reduced antigen presentation to cytotoxic lymphocytes.
