Angiotensin-(1-7) inhibits the migration and invasion of A549 human lung adenocarcinoma cells through inactivation of the PI3K/Akt and MAPK signaling pathways

The local renin-angiotensin system (RAS) is one of the crucial componentsin the tumor microenvironment. Recent evidence suggests that the local RAS playsan important role in tumor metabolism, survival, angiogenesis and invasion processes.Angiotensin-(1-7) [Ang-(1-7)] is an endogenous peptide of the RAS with vasodilatorand anti-proliferative properties. Previous studies have demonstrated that Ang-(1-7)inhibits both the growth of human lung cancer cells in vitro and tumor angiogenesisin vivo through activation of the MAS receptor. This study investigated the anti-metastaticeffect of Ang-(1-7) in A549 human lung adenocarcinoma cells in vitro. We foundthat Ang-(1-7) reduced the cell migratory and invasive abilities by reducing theexpression and activity of MMP-2 and MMP-9. Furthermore, we demonstrated thatthe anti-migration and anti-invasion effect of Ang-(1-7) was mediated throughinactivation of the PI3K/Akt, P38 and JNK signal pathways. Our results suggestthat Ang-(1-7) may have therapeutic potential against advanced lung carcinomaas a new agent.