Satoshi Owada1, Kanako Ito1, Hitoshi Endo1, Yukari Shida1, Chisa Okada2, Takahiro Nezu1, Masayuki Tatemichi3. 1. Center for Molecular Prevention and Environmental Medicine, Department of Preventive Medicine, Tokai University School of Medicine, Isehara, Japan. 2. Support Center for Medical Research and Education, Tokai University, Isehara, Japan. 3. Center for Molecular Prevention and Environmental Medicine, Department of Preventive Medicine, Tokai University School of Medicine, Isehara, Japan tatemichi@tokai.ac.jp.
Abstract
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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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. Copyright
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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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. Copyright