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

Oncol Rep. 2012 Mar;27(3):783-90. doi: 10.3892/or.2011.1554. Epub 2011 Nov 15.


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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / blood supply
  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Adenocarcinoma of Lung
  • Angiotensin I / pharmacology*
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects
  • Humans
  • Lung Neoplasms / blood supply
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • MAP Kinase Signaling System / drug effects*
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors*
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Neoplasm Invasiveness
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / metabolism
  • Peptide Fragments / pharmacology*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors*
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Renin-Angiotensin System / drug effects
  • Signal Transduction / drug effects
  • Survival


  • Peptide Fragments
  • Phosphoinositide-3 Kinase Inhibitors
  • Angiotensin I
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinase Kinases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • angiotensin I (1-7)