Autophagy enhanced the radioresistance of non-small cell lung cancer by regulating ROS level under hypoxia condition
Autophagy enhanced the radioresistance of non-small cell lung cancer by regulating ROS level under hypoxia condition
复制标题
自噬通过调节低氧条件下ROS水平增强非小细胞肺癌的放射抵抗
DOI：
10.1080/09553002.2017.1325025
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发表时间：
2017-01-01
影响因子：
2.6
通讯作者：
Shao, Chunlin
中科院分区：
文献类型：
--
作者：
Chen, Xiaoyan;Wang, Ping;Shao, Chunlin
摘要 目的：肿瘤对放射线的抵抗力一直是肺癌预后不良的一大障碍。据报道，缺氧和自噬在一定程度上导致了这种抵抗。然而，自噬在癌症治疗中是否发挥积极作用尚存在争议。我们的目标是找出抗辐射的具体机制。材料和方法：A549细胞在照射前用条件培养基（CM）在缺氧或常氧条件下处理12小时，然后测量克隆形成存活、活性氧（ROS）、线粒体信号和自噬通量。在一些实验中，A549细胞分别转染LC3小干扰RNA（siRNA），或用厄尔平衡盐溶液（EBSS）处理。结果：我们发现缺氧通过增加自噬的诱导来增强细胞的放射抗性。缺氧应激后，线粒体数量减少，但细胞内ROS水平升高。值得注意的是，自噬可能通过缺氧治疗期间减少ROS来增强细胞的放射抗性。结论：我们阐明了自噬调节癌细胞死亡或存活的可能机制。这些结果为缺氧肿瘤放射抵抗的内在因素提供了新的认识。
Abstract Purpose: Tumor resistance towards radiation has been a big obstacle in the poor prognosis of lung cancer. It has been reported that hypoxia and autophagy partly contribute to this resistance. However, there is controversy over whether autophagy plays a positive role in cancer therapy or not. We aim to find out the specific mechanism of radiation resistance. Materials and methods: A549 cells were treated with conditioned medium (CM) under 12 h hypoxia or normoxia before irradiation, followed by the measurement of clonogenic survival, reactive oxygen species (ROS), signal of mitochondria and autophagy flux. In some experiments, the A549 cells were respectively transfected with LC3 small interfering RNA (siRNA), or treated with Earle’s Balanced Salt Solution (EBSS). Results: We found that hypoxia enhanced cell radioresistance by increasing the induction of autophagy. And after hypoxia stress, the number of mitochondria was reduced but the cellular ROS level was enhanced. It was significant that autophagy may enhance cell radioresistance by reducing ROS during hypoxic treatment. Conclusions: We elucidated the possible mechanisms of autophagy in regulating cancer cell death or survival. These results supply a new opinion about the intrinsic factor of radioresistance of hypoxia tumors.