Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Curr Mol Med. 2013 Jul;13(6):1023-34. doi: 10.2174/15665240113139990055.
The purpose of this study was to test the hypothesis that chronic stress in a negative social and psychological state plays a critical role in pancreatic cancer development and progression. In this study, we created a new stress model system to determine the effects of chronic stress on pancreatic cancer progression. Here, we show that chronic stress not only causes depression in mice, most likely attributed to an elevated level of epinephrine, but also induces pancreatic cancer progression. We provide evidence that the pancreatic cancer progression induced by chronic stress could be blocked to a significant degree by β2-AR inhibitor ICI118 551 or HIF-1α inhibitor 2-methoxyestradiol. Moreover, establishment of pancreatic cancer in mice exposed to chronic stress was accompanied by up-regulation of the expression of MMP-2, MMP-9, and VEGF, mediated by a HIF- 1α-dependent β-AR signaling pathway. Our data suggest that the β2-AR-HIF-1α axis regulates stress-induced pancreatic tumor growth and angiogenesis. This study may have a therapeutic or preventive potential for the patients with pancreatic cancer who are especially prone to psychosocial stress challenges.
本研究旨在验证下述假说，即负性社会心理状态下的慢性应激在胰腺癌的发生和发展中起关键作用。在本研究中，我们构建了一个新的应激模型系统，以确定慢性应激对胰腺癌进展的影响。我们发现，慢性应激不仅导致小鼠抑郁，很可能是由于肾上腺素水平升高所致，而且还会诱发胰腺癌进展。我们的证据表明，β2-AR 抑制剂 ICI118551 或 HIF-1α 抑制剂 2-甲氧基雌二醇可在很大程度上阻断慢性应激引起的胰腺癌进展。此外，在慢性应激暴露的小鼠中建立胰腺癌时，MMP-2、MMP-9 和 VEGF 的表达上调，这是由 HIF-1α 依赖的β-AR 信号通路介导的。我们的数据表明，β2-AR-HIF-1α 轴调节应激诱导的胰腺肿瘤生长和血管生成。本研究可能为易受心理社会应激挑战的胰腺癌患者提供治疗或预防的潜力。
