Owada Satoshi, Ito Kanako, Endo Hitoshi, Shida Yukari, Okada Chisa, Nezu Takahiro, Tatemichi Masayuki
Center for Molecular Prevention and Environmental Medicine, Department of Preventive Medicine, Tokai University School of Medicine, Isehara, Japan.
Support Center for Medical Research and Education, Tokai University, Isehara, Japan.
Anticancer Res. 2017 Sep;37(9):4927-4934. doi: 10.21873/anticanres.11902.
BACKGROUND/AIM: Pancreatic cancer tissue is a hypoxic environment resistant to anticancer drugs. This study examined the role of autophagy as a response to hypoxic stress in pancreatic cancer.
Pancreatic cell lines (PANC-1, BxPC-3 and AsPC-1) were exposed to hypoxic conditions using cobalt chloride, a hypoxia-mimicking agent. Protein expression and cytotoxicity assays were performed to determine the effect of hypoxia on autophagy.
When pancreatic cancer cells were exposed to hypoxia, autophagy was induced. The autophagy-inducing signal was dependent on the AMPK pathway. Inhibition of autophagy in a hypoxic state induced a remarkable cytotoxicity and enhanced apoptosis. When an AMPK inhibitor was added, cytotoxicity was observed in the hypoxic environment.
The induced autophagy, dependent on the AMPK pathway, is a necessary survival strategy adopted by pancreatic cancer cells to adapt to hypoxic stress, and could be an attractive target for drug development.
背景/目的：胰腺癌组织是对抗癌药物具有抗性的缺氧环境。本研究探讨自噬在胰腺癌缺氧应激反应中的作用。
使用缺氧模拟剂氯化钴将胰腺癌细胞系（PANC-1、BxPC-3和AsPC-1）暴露于缺氧条件下。进行蛋白质表达和细胞毒性测定以确定缺氧对自噬的影响。
当胰腺癌细胞暴露于缺氧环境时，自噬被诱导。自噬诱导信号依赖于AMPK途径。在缺氧状态下抑制自噬会诱导显著的细胞毒性并增强凋亡。当添加AMPK抑制剂时，在缺氧环境中观察到细胞毒性。
依赖于AMPK途径诱导的自噬是胰腺癌细胞为适应缺氧应激而采取的必要生存策略，并且可能成为药物开发的有吸引力的靶点。
