Angiotensin-(1-7) Decreases Cell Growth and Angiogenesis of Human Nasopharyngeal Carcinoma Xenografts
Angiotensin-(1-7) Decreases Cell Growth and Angiogenesis of Human Nasopharyngeal Carcinoma Xenografts
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DOI：
10.1158/1535-7163.mct-14-0981
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发表时间：
2016-01-01
影响因子：
5.7
通讯作者：
Li, Hongwei
中科院分区：
文献类型：
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作者：
Pei, Nana;Wan, Renqiang;Li, Hongwei
血管紧张素-（1-7）[Ang-（1-7）]是一种通过Mas受体（MasR）起作用的内源性七肽激素，具有抗增殖和抗血管生成特性。最近的研究表明，Ang-（1-7）对肺腺癌细胞和前列腺癌细胞具有抗增殖作用。在这项研究中，我们报告MasR水平显着上调，在鼻咽癌（NPC）标本和NPC细胞系。病毒载体介导的Ang-（1-7）表达显著抑制鼻咽癌细胞的增殖和迁移。这些作用可被特异性Ang-（1-7）受体拮抗剂A-779完全阻断，提示它们是由Ang-（1-7）受体Mas介导的。在这项研究中，Ang-（1-7）不仅引起人鼻咽异种移植物生长的显著减少，而且还显著降低血管密度，表明七肽抑制血管生成以减小肿瘤大小。机制研究表明，Ang-（1-7）抑制促血管生成因子VEGF和PlGF的表达。综上所述，数据表明MasR的上调可用作NPC的诊断标志物，并且Ang-（1-7）可能是用于鼻咽癌治疗的新的治疗剂，因为其具有显著的抗血管生成活性。(C)2015年AACR。
Angiotensin-(1-7) [Ang-(1-7)] is an endogenous, heptapeptide hormone acting through the Mas receptor (MasR), with antiproliferative and antiangiogenic properties. Recent studies have shown that Ang-(1-7) has an antiproliferative action on lung adenocarcinoma cells and prostate cancer cells. In this study, we report that MasR levels were significantly upregulated in nasopharyngeal carcinoma (NPC) specimens and NPC cell lines. Viral vector-mediated expression of Ang-(1-7) dramatically suppressed NPC cell proliferation and migration in vitro. These effects were completely blocked by the specific Ang-(1-7) receptor antagonist A-779, suggesting that they are mediated by the Ang-(1-7) receptor Mas. In this study, Ang-(1-7) not only caused a significant reduction in the growth of human nasopharyngeal xenografts, but also markedly decreased vessel density, suggesting that the heptapeptide inhibits angiogenesis to reduce tumor size. Mechanistic investigations revealed that Ang-(1-7) inhibited the expression of the proangiogenic factors VEGF and PlGF. Taken together, the data suggest that upregulation of MasR could be used as a diagnostic marker of NPC and Ang-(1-7) may be a novel therapeutic agent for nasopharyngeal cancer therapy because it exerts significant antiangiogenic activity. (C) 2015 AACR.