Department of Gastroenterology, The First Affiliated Hospital, Zhengzhou University School of Medicine, Zhengzhou 450052, China; Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No. 197, Ruijin Er Road, Shanghai 200025, China.
Department of Respiratory Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China.
Cancer Lett. 2011 Aug 1;307(1):18-25. doi: 10.1016/j.canlet.2011.03.011. Epub 2011 Apr 9.
Angiotensin-converting enzyme 2 (ACE2) is a novel component of the renin-angiotensin system that could counterbalance the growth-promoting function of angiotensin-converting enzyme (ACE). Our previous results have shown that ACE2 is lowly expressed in pancreas, and widely down-regulated in pancreatic cancer tissues and cells. In the present study, we investigated the effect of restoration of ACE2 expression on the growth of pancreatic cancer. We found that restoration of ACE2 protein suppressed cell proliferation, motility and increased the sensitivity to hypoxia induced injury in BxPC3 and SW1990 cell lines. Stably transfected cells overexpressing ACE2 exhibited decreased tumorigenicity and delayed tumor growth, both in vitro and in vivo. In addition, restoration of ACE2 expression mediated by adenovirus vector significantly inhibited the established tumor growth, strongly enhanced the anti-tumor activity of gemcitabine in a pancreatic cancer xenograft model in vivo, and significantly prolonged the survival time of animals bearing tumor xenografts. These results provide evidence that ACE2 plays a pivotal role in the development of pancreatic cancer, and suggest that ACE2 is a promising candidate for pancreatic cancer treatment.
血管紧张素转换酶 2（ACE2）是肾素-血管紧张素系统的一个新组成部分，它可以抵消血管紧张素转换酶（ACE）的促生长作用。我们之前的研究结果表明，ACE2 在胰腺中表达水平较低，并且在胰腺癌组织和细胞中广泛下调。在本研究中，我们研究了恢复 ACE2 表达对胰腺癌生长的影响。我们发现 ACE2 蛋白的恢复抑制了 BxPC3 和 SW1990 细胞系的细胞增殖、迁移，并增加了对缺氧诱导损伤的敏感性。过表达 ACE2 的稳定转染细胞表现出体外和体内肿瘤生成能力降低和肿瘤生长延迟。此外，腺病毒载体介导的 ACE2 表达恢复显著抑制了已建立的肿瘤生长，在体内胰腺癌异种移植模型中强烈增强了吉西他滨的抗肿瘤活性，并显著延长了携带肿瘤异种移植物的动物的存活时间。这些结果提供了证据表明 ACE2 在胰腺癌的发展中起关键作用，并表明 ACE2 是治疗胰腺癌的有前途的候选药物。
