Genistein sensitizes sarcoma cells in vitro and in vivo by enhancing apoptosis and by inhibiting DSB repair pathways.
Genistein sensitizes sarcoma cells in vitro and in vivo by enhancing apoptosis and by inhibiting DSB repair pathways.
复制标题
金雀异黄素通过增强细胞凋亡和抑制 DSB 修复途径在体外和体内使肉瘤细胞变得敏感
DOI：
10.1093/jrr/rrv091
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发表时间：
2016-06
影响因子：
2
通讯作者：
Li Q
中科院分区：
文献类型：
--
作者：
Liu XX;Sun C;Jin XD;Li P;Zheng XG;Zhao T;Li Q
本研究旨在探讨染料木黄酮对小鼠肉瘤细胞的放射增敏作用及其生物学机制。使用无毒剂量10 μM染料木黄酮，X射线照射后S180细胞50%存活率的增敏比（IC_（50））为1.45。对于用染料木黄酮和X射线共治疗的小鼠，与对照组和仅照射组相比，切除的肿瘤组织具有减少的血管和减小的大小和体积。此外，凋亡的显著增加伴随着线粒体中Bax的上调和Bcl-2的下调，以及大量的细胞色素c被转移到细胞质中。此外，X射线联合染料木素抑制DNA-PKcs的活性，使DNA损伤位点以Ku 70/80为主，导致同源重组（HR）和非同源末端连接（NHEJ）修复不完全，最终导致细胞凋亡。我们的研究，第一次，证明染料木素敏化肉瘤细胞的X射线，这种放射增敏作用依赖于诱导线粒体凋亡途径和抑制双链断裂（DSB）修复途径。
The aim of this work was to investigate the radiosensitization effects of genistein on mice sarcoma cells and the corresponding biological mechanisms in vitro and in vivo. Using the non-toxic dosage of 10 μM genistein, the sensitizer enhancement ratios after exposure to X-rays at 50% cell survival (IC50) was 1.45 for S180 cells. For mice cotreated with genistein and X-rays, the excised tumor tissues had reduced blood vessels and decreased size and volume compared with the control and irradiation-only groups. Moreover, a significant increase in apoptosis was accompanied by upregulation of Bax and downregulation of Bcl-2 in the mitochondria, and lots of cytochrome c being transferred to the cytoplasm. Furthermore, X-rays combined with genistein inhibited the activity of DNA-PKcs, so DNA-injured sites were dominated by Ku70/80, leading to incompleteness of homologous recombination (HR) and non-homologous end-joining (NHEJ) repairs and the eventual occurrence of cell apoptosis. Our study, for the first time, demonstrated that genistein sensitized sarcoma cells to X-rays and that this radiosensitizing effect depended on induction of the mitochondrial apoptosis pathway and inhibition of the double-strand break (DSB) repair pathways.