Angiotensin 1-7 and the Non-Peptide MAS-R Agonist AVE0991 Inhibit Breast Cancer Cell Migration and Invasion

Background: Endocrine resistance in breast cancer is associated with the epithelial-to-mesenchymal transition (EMT), resulting in enhanced cell proliferation, motility, and invasion and leading to a poor prognosis. There are few studies regarding the role of Angiotensin II (Ang II) and Angiotensin 1-7 (Ang 1-7) in relation to breast cancer, with contradictory outcomes. This study aims to investigate the expression of Ang 1-7 and MAS-R and evaluate the effects of Ang II, Ang 1-7, and the MAS-R agonist AVE0991 on EMT induction and reversal. Methods: The effects of Ang II and Ang 1-7 on normal and breast cancer cell lines were determined using various techniques for cell proliferation (MTT), motility (scratch assay), and invasion (Cultrex assay). Also, the expression/localization profiles of Ang 1-7 and its receptor (MAS-R), as well as various EMT markers, were determined using immunofluorescence, western blot, and ELISA. Results: Ang II significantly decreased the motility of the tested cell lines; however, it did not have a significant effect on their proliferation or invasion. The expression profiles of the tested EMT markers were not affected by Ang II treatment. The expression levels of Ang 1-7 and MAS-R were significantly higher in the normal breast epithelial cells and estrogen receptor ER compared to the ER+ breast cancer cells. Treatment with Ang 1-7 or the non-peptide MAS-R agonist AVE0991 significantly reduced the migration and invasion of the tested cell lines without modulating the tested EMT markers. Compared to Ang 1-7, AVE0991 exhibited a more prominent dose-dependent inhibitory effect on the proliferation, motility, and invasion of the ER- breast cancer cells. Conclusions: Ang 1-7 and AVE0991 play a promising therapeutic role in breast cancer, in part by reducing cell motility and invasion.