期刊
MOLECULAR MEDICINE
卷 21, 期 -, 页码 626-636出版社
SPRINGER
DOI: 10.2119/molmed.2015.00022
关键词
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资金
- National 973 Basic Research Program of China [2011CB503906, 2012CB518603]
- National High-Tech Research and Development Program of China [2012AA02A510]
- Program of Introducing Talents of Discipline to Universities [B07035]
- State Program of National Natural Science Foundation of China for Innovative Research Group [81021001]
- National Natural Science Foundation of China [81400284, 81371548, 81320108004, 61331001]
- Natural Science Foundation of Shandong Province [ZR2014HM044, ZR2014HP045]
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.
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