Hu Lelin, Wang Hao, Huang Li, Zhao Yong, Wang Junjie
Department of Radiation Oncology, Peking University 3rd Hospital, Haidian District, Beijing 100191, China; School of Medicine, Anhui University of Science and Technology, Huainan 232001, Anhui, China.
Department of Radiation Oncology, Peking University 3rd Hospital, Haidian District, Beijing 100191, China.
Oxid Med Cell Longev. 2016;2016:9460462. doi: 10.1155/2016/9460462. Epub 2016 Dec 29.
For many unresectable carcinomas and locally recurrent cancers (LRC), I seeds brachytherapy is a feasible, effective, and safe treatment. Several studies have shown that I seeds radiation exerts anticancer activity by triggering DNA damage. However, recent evidence shows mitochondrial quality to be another crucial determinant of cell fate, with mitophagy playing a central role in this control mechanism. Herein, we found that I seeds irradiation injured mitochondria, leading to significantly elevated mitochondrial and intracellular ROS (reactive oxygen species) levels in HCT116 cells. The accumulation of mitochondrial ROS increased the expression of HIF-1 and its target genes BINP3 and NIX (BINP3L), which subsequently triggered mitophagy. Importantly, I seeds radiation induced mitophagy promoted cells survival and protected HCT116 cells from apoptosis. These results collectively indicated that I seeds radiation triggered mitophagy by upregulating the level of ROS to promote cellular homeostasis and survival. The present study uncovered the critical role of mitophagy in modulating the sensitivity of tumor cells to radiation therapy and suggested that chemotherapy targeting on mitophagy might improve the efficiency of I seeds radiation treatment, which might be of clinical significance in tumor therapy.
对于许多无法切除的癌和局部复发性癌症（LRC），碘-125籽源近距离放射治疗是一种可行、有效且安全的治疗方法。多项研究表明，碘-125籽源辐射通过引发DNA损伤发挥抗癌活性。然而，最近的证据表明线粒体质量是细胞命运的另一个关键决定因素，其中线粒体自噬在这种控制机制中起核心作用。在此，我们发现碘-125籽源照射会损伤线粒体，导致HCT116细胞中的线粒体和细胞内活性氧（ROS）水平显著升高。线粒体ROS的积累增加了HIF-1及其靶基因BINP3和NIX（BINP3L）的表达，随后引发线粒体自噬。重要的是，碘-125籽源辐射诱导的线粒体自噬促进了细胞存活，并保护HCT116细胞免于凋亡。这些结果共同表明，碘-125籽源辐射通过上调ROS水平触发线粒体自噬，以促进细胞内稳态和存活。本研究揭示了线粒体自噬在调节肿瘤细胞对放射治疗敏感性中的关键作用，并表明针对线粒体自噬的化疗可能提高碘-125籽源放射治疗的效率，这在肿瘤治疗中可能具有临床意义。
