Hu Lelin, Wang Hao, Huang Li, Zhao Yong, Wang Junjie
Department of Radiation Oncology, Peking University Third Hospital, Haidian, Beijing 100191, P.R. China.
State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, P.R. China.
Int J Oncol. 2016 Dec;49(6):2217-2226. doi: 10.3892/ijo.2016.3719. Epub 2016 Oct 5.
Autophagy induced by radiation is critical to cell fate decision. Evidence now sheds light on the importance of autophagy induced by cancer radiotherapy. Traditional view considers radiation can directly or indirectly damage DNA which can activate DNA damage the repair signaling pathway, a large number of proteins participating in DNA damage repair signaling pathway such as p53, ATM, PARP1, FOXO3a, mTOR and SIRT1 involved in autophagy regulation. However, emerging recent evidence suggests radiation can also cause injury to extranuclear targets such as plasma membrane, mitochondria and endoplasmic reticulum (ER) and induce accumulation of ceramide, ROS, and Ca2+ concentration which activate many signaling pathways to modulate autophagy. Herein we review the role of autophagy in radiation therapy and the potent intracellular autophagic triggers induced by radiation. We aim to provide a more theoretical basis of radiation-induced autophagy, and provide novel targets for developing cytotoxic drugs to increase radiosensitivity.
辐射诱导的自噬对细胞命运的决定至关重要。目前的证据揭示了癌症放射治疗诱导自噬的重要性。传统观点认为，辐射可直接或间接损伤DNA，进而激活DNA损伤修复信号通路，大量参与DNA损伤修复信号通路的蛋白质，如p53、ATM、PARP1、FOXO3a、mTOR和SIRT1，均参与自噬调节。然而，最近新出现的证据表明，辐射还可导致对细胞核外靶点（如质膜、线粒体和内质网）的损伤，并诱导神经酰胺、活性氧和钙离子浓度的积累，从而激活许多信号通路来调节自噬。在此，我们综述了自噬在放射治疗中的作用以及辐射诱导的有效的细胞内自噬触发因素。我们旨在为辐射诱导的自噬提供更多的理论基础，并为开发细胞毒性药物以提高放射敏感性提供新的靶点。
