Department of Pharmacology, Toxicology and Therapeutics, School of Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA.
J Cell Biochem. 2013 Jan;114(1):192-203. doi: 10.1002/jcb.24354.
In a recent study, we showed that eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), two common omega-3 fatty acids, can cause ROS accumulation and subsequently induce caspase-8-dependent apoptosis in human breast cancer cells (Kang et al. [2010], PLoS ONE 5: e10296). In this study, we showed that the pancreas has a unique ability to accumulate EPA at a level markedly higher than several other tissues analyzed. Based on this finding, we sought to further investigate the anticancer actions of EPA and its analog DHA in human pancreatic cancer cells using both in vitro and in vivo models. EPA and DHA were found to induce ROS accumulation and caspase-8-dependent cell death in human pancreatic cancer cells (MIA-PaCa-2 and Capan-2) in vitro. Feeding animals with a diet supplemented with 5% fish oil, which contains high levels of EPA and DHA, also strongly suppresses the growth of MIA-PaCa-2 human pancreatic cancer xenografts in athymic nude mice, by inducing oxidative stress and cell death. In addition, we showed that EPA can concomitantly induce autophagy in these cancer cells, and the induction of autophagy diminishes its ability to induce apoptotic cell death. It is therefore suggested that combination of EPA with an autophagy inhibitor may be a useful strategy in increasing the therapeutic effectiveness in pancreatic cancer.
在最近的一项研究中，我们表明二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）这两种常见的ω-3 脂肪酸可导致 ROS 积累，并随后诱导人乳腺癌细胞中的 caspase-8 依赖性细胞凋亡（Kang 等人，[2010]，PLoS ONE 5:e10296）。在这项研究中，我们表明胰腺具有独特的能力，可使 EPA 积累到明显高于其他几种分析组织的水平。基于这一发现，我们试图使用体外和体内模型进一步研究 EPA 及其类似物 DHA 对人胰腺癌细胞的抗癌作用。在体外，EPA 和 DHA 可诱导人胰腺癌细胞（MIA-PaCa-2 和 Capan-2）中 ROS 积累和 caspase-8 依赖性细胞死亡。用含有高水平 EPA 和 DHA 的 5%鱼油饮食喂养动物，也可通过诱导氧化应激和细胞死亡，强烈抑制裸鼠中 MIA-PaCa-2 人胰腺癌细胞异种移植物的生长。此外，我们表明 EPA 可同时诱导这些癌细胞发生自噬，而自噬的诱导会降低其诱导凋亡性细胞死亡的能力。因此，建议将 EPA 与自噬抑制剂联合使用可能是增加胰腺癌治疗效果的有效策略。
