The angiotensin-converting enzyme 2 in tumor growth and tumor-associated angiogenesis in non-small cell lung cancer
The angiotensin-converting enzyme 2 in tumor growth and tumor-associated angiogenesis in non-small cell lung cancer
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DOI：
10.3892/or_00000718
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发表时间：
2010-04-01
期刊：
影响因子：
4.2
通讯作者：
Qiu, Weicheng
中科院分区：
文献类型：
--
作者：
Feng, Yun;Wan, Huanying;Qiu, Weicheng
血管紧张素II （Angiotensin II, AnoII）是一种多功能的生物活性肽，已有研究表明，宿主和肿瘤的肾素-血管紧张素系统（renin-angiotensin system， RAS）在肺癌的肿瘤生长和血管生成中都起重要作用。血管紧张素转换酶2 （angiotensin converting enzyme, ACE2）是RAS中一个新发现的成分，与ACE有42%的氨基酸同源性。然而，ACE2在非小细胞肺癌（NSCLC）中的表达和功能尚不清楚。在本研究中，我们采用Western blot分析和免疫组化分析ACE2在NSCLC组织中的表达。用放射免疫法检测组织匀浆中AngII的浓度。我们还通过用MSCV-ACE2转导A549细胞来检测ACE2的功能。我们首次表明，在AngII高于匹配的非恶性组织的NSCLC组织中，ACE2表达降低。浓度为10(-6)mol/l的AngII显著提高血管内皮生长因子A （VEGFa）和ATI-R的表达，降低ACE2的表达。我们还发现，ACE2的过表达可能通过抑制细胞生长和体外VEGFa的产生而具有保护作用。ACE2可能成为治疗非小细胞肺癌新策略的靶点。
Angiotensin II (AnoII) is a Multifunctional bioactive peptide and previous studies have shown that the renin-angiotensin system (RAS) of both host and tumor are important in tumor growth and angiogenesis in lung cancer. Angiotensin-converting enzyme 2 (ACE2) is a newly identified component of RAS, with 42% amino acid homology, to ACE. However, the expression and function of ACE2 in non-small cell lung cancer (NSCLC) are Still unclear. In the present study, we analyzed ACE2 expression in NSCLC tissue by Western blot analysis and immunohitochemistry. AngII concentrations in the tissue homogenate were also detected Using radio- immunoassay. We also examined the function of ACE2 by transducing A549 cells with MSCV-ACE2. We have shown for the first time that ACE2 expression decreased in NSCLC tissue in which AngII was higher than the matching non-malignant tissues. A concentration of 10(-6) mol/l of AngII significantly increased expression of vascular endothelial growth factor a (VEGFa) and ATI-R and decreased ACE2 expression. We also found that overexpression of ACE2 may have a protective effect by inhibiting cell growth and VEGFa production in vitro. ACE2 may become a target of novel strategies to treat NSCLC.