Inhibitory effect of the peptide epitalon on the development of spontaneous mammary tumors in HER‐2/neu transgenic mice

Female FVB/N HER‐2/neu transgenic mice from the age of 2 months were subcutaneously injected with saline, the peptide Epitalon® (Ala‐Glu‐Asp‐Gly) or with the peptide Vilon® (Lys‐Glu) in a single dose of 1 μg/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. © 2002 Wiley‐Liss, Inc.