Huber Stephan M, Butz Lena, Stegen Benjamin, Klumpp Lukas, Klumpp Dominik, Eckert Franziska
Department of Radiation Oncology, University of Tübingen, Germany.
Department of Radiation Oncology, University of Tübingen, Germany; Department of Pharmacology, Toxicology and Clinical Pharmacy, Institute of Pharmacy, University of Tübingen, Germany.
Biochim Biophys Acta. 2015 Oct;1848(10 Pt B):2657-64. doi: 10.1016/j.bbamem.2014.11.004. Epub 2014 Nov 15.
Neoadjuvant, adjuvant or definitive fractionated radiation therapy are implemented in first line anti-cancer treatment regimens of many tumor entities. Ionizing radiation kills the tumor cells mainly by causing double strand breaks of their DNA through formation of intermediate radicals. Survival of the tumor cells depends on both, their capacity of oxidative defense and their efficacy of DNA repair. By damaging the targeted cells, ionizing radiation triggers a plethora of stress responses. Among those is the modulation of ion channels such as Ca2+-activated K+ channels or Ca2+-permeable nonselective cation channels belonging to the super-family of transient receptor potential channels. Radiogenic activation of these channels may contribute to radiogenic cell death as well as to DNA repair, glucose fueling, radiogenic hypermigration or lowering of the oxidative stress burden. The present review article introduces these channels and summarizes our current knowledge on the mechanisms underlying radiogenic ion channel modulation. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers.
新辅助、辅助或根治性分割放射治疗被应用于许多肿瘤实体的一线抗癌治疗方案中。电离辐射主要通过形成中间自由基导致肿瘤细胞DNA双链断裂来杀死肿瘤细胞。肿瘤细胞的存活取决于其氧化防御能力和DNA修复效率。通过损伤靶细胞，电离辐射引发大量应激反应。其中包括对离子通道的调节，如钙激活钾通道或属于瞬时受体电位通道超家族的钙通透非选择性阳离子通道。这些通道的放射源性激活可能有助于放射源性细胞死亡以及DNA修复、葡萄糖供应、放射源性超迁移或减轻氧化应激负担。本综述文章介绍了这些通道，并总结了我们目前对放射源性离子通道调节潜在机制的认识。本文是名为“癌症中的膜通道和转运体”的特刊的一部分。
