Angiotensin-(1-7) significantly reduced human lung tumor growth, vessel density, and neovascularization (>50% decrease), likely by reducing vascular endothelial growth factor-A.
Does Angiotensin-(1-7) inhibit tumor angiogenesis and reduce tumor size in human lung cancer xenografts?
Angiotensin-(1-7) exhibits significant antiangiogenic activity by reducing VEGF-A and may serve as a novel therapeutic agent targeting the AT(1-7) receptor for lung cancer.
Angiotensin-(1-7) Ang-(1-7) is an endogenous seven-amino acid peptide hormone with antiproliferative properties. Our previous studies showed that Ang-(1-7) inhibits the growth of human lung cancer cells in vitro and reduces the size of human lung tumor xenografts in vivo. In the current study, s.c. injection of Ang-(1-7) not only caused a significant reduction in human A549 lung tumor growth but also markedly decreased vessel density, suggesting that the heptapeptide inhibits angiogenesis to reduce tumor size. A decrease in human endothelial cell tubule formation in Matrigel was observed following a 16 h incubation with Ang-(1-7), with a maximal reduction at a 10 nmol/L concentration. Ang-(1-7) had similar antiangiogenic effects in the chick chorioallantoic membrane, causing a >50% decrease in neovascularization. The Ang-(1-7)-induced reduction in both endothelial cell tubule formation and vessel formation in the chick was completely blocked by the specific Ang-(1-7) receptor antagonist d-proline(7)-Ang-(1-7), suggesting that these biological actions are mediated by an AT((1-7)) receptor. Ang-(1-7) significantly reduced vascular endothelial growth factor-A protein and mRNA in tumors from mice treated with the heptapeptide compared with saline controls as well as in the parent A549 human lung cancer cells in culture. These results suggest that Ang-(1-7) may attenuate tumor angiogenesis by reducing vascular endothelial growth factor-A, a primary proangiogenic protein. Taken together, this study shows that Ang-(1-7) exhibits significant antiangiogenic activity and may be a novel therapeutic agent for lung cancer treatment targeting a specific AT((1-7)) receptor.
Soto‐Pantoja et al. (Mon,) conducted a other in Human lung cancer. Angiotensin-(1-7) vs. Saline controls was evaluated on Tumor growth, vessel density, and neovascularization. Angiotensin-(1-7) significantly reduced human lung tumor growth, vessel density, and neovascularization (>50% decrease), likely by reducing vascular endothelial growth factor-A.