Angiotensin-(1-7) Suppresses Hepatocellular Carcinoma Growth and Angiogenesis via Complex Interactions of Angiotensin II Type 1 Receptor, Angiotensin II Type 2 Receptor and Mas Receptor

作者：Liu, Yanping; Li, Bin; Wang, Ximing; Li, Guishuang; Shang, Rui; Yang, Jianmin; Wang, Jiali; Zhang, Meng; Chen, Yuguo; Zhang, Yun; Zhang, Cheng; Hao, Panpan^*

来源：Molecular Medicine, 2015, 21: 626-636.

DOI：10.2119/molmed.2015.00022

• HYPOXIA-INDUCIBLE FACTOR-1-ALPHA
• TUMOR ANGIOGENESIS
• PROSTATE-CANCER
• INHIBITS GROWTH
• BREAST-CANCER
• MICROVESSEL DENSITY
• CELL PROLIFERATION
• APOPTOSIS
• EXPRESSION
• TARGET

We recently confirmed that angiotensin II (Ang II) type 1 receptor (AT(1)R) was overexpressed in hepatocellular carcinoma tissue using a murine hepatoma model. Angiotensin(Ang)-(1-7) has been found beneficial in ameliorating lung cancer and prostate cancer. Which receptor of Ang-(1-7) is activated to mediate its effects is much speculated. This study was designed to investigate the effects of Ang-(1-7) on hepatocellular carcinoma, as well as the probable mechanisms. H22 hepatoma-bearing mice were randomly divided into five groups for treatment: mock group, low-dose Ang-(1-7), high-dose Ang-(1-7), high-dose Ang-(1-7) + A779 and high-dose Ang-(1-7) + PD123319. Ang-(1-7) treatment inhibited tumor growth time- and dose-dependently by arresting tumor proliferation and promoting tumor apoptosis as well as inhibiting tumor angiogenesis. The effects of Ang-(1-7) on tumor proliferation and apoptosis were reversed by coadministration with A779 or PD123319, whereas the effects on tumor angiogenesis were completely reversed by A779 but not by PD123319. Moreover, Ang-(1-7) downregulated AT(1)R mRNA, upregulated mRNA levels of Ang II type 2 receptor (AT(2)R) and Mas receptor (MasR) and p38-MAPK phosphorylation and suppressed H22 cell-endothelial cell communication. Thus, Ang-(1-7) administration suppresses hepatocellular carcinoma via complex interactions of AT(1)R, AT(2)R and MasR and may provide a novel and promising approach for the treatment of hepatocellular carcinoma.

• 出版日期2015
• 单位济南市中心医院; 山东省医学影像学研究所; 山东大学