Angiotensin-converting enzyme 2 acts as a potential molecular target for pancreatic cancer therapy

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.