首页> 外文期刊>Journal of Pharmaceutics >Cellular Redox Status Regulates Emodin-Induced Radiosensitization of Nasopharyngeal Carcinoma Cells In Vitro and In Vivo
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Cellular Redox Status Regulates Emodin-Induced Radiosensitization of Nasopharyngeal Carcinoma Cells In Vitro and In Vivo

机译:细胞氧化还原状态调节大黄素诱导的鼻咽癌细胞体外和体内放射增敏作用。

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Here, we report that regulation of cellular redox status is required for radiosensitization of nasopharyngeal carcinoma (NPC) cells by emodin. We evaluated emodin’s radiosensitivity-enhancing ability by using NPC cells in vitro and xenografts in vivo. A clonogenic assay was performed to evaluate NPC cell survival and to determine dose modification factors. Flow cytometry, western blot analysis, and in vivo radiation-induced tumor regrowth delay assays were performed to characterize emodin’s effects. Exposure of CNE-1 NPC cells to emodin enhanced their radiosensitivity. HIF-1αexpression significantly increased under hypoxic conditions but did not change after treatment with emodin alone. Emodin downregulated mRNA and protein expression of HIF-1α. Cells exposed to radiation and emodin underwent significant cell cycle arrest at the G2/M phase. The percentage of apoptotic cells and reactive oxygen species (ROS) levels were significantly higher in the group exposed to emodin and radiation hypoxic group than in the other groups. Compared to the CNE-1 xenografts exposed to radiation alone, CNE-1 xenografts exposed to radiation with emodin showed significantly enhanced radiation effects. Our data suggest that emodin effectively enhanced the radiosensitivity of CNE-1 cells in vitro and in vivo. The mechanism appears to involve ROS generation and ROS-mediated inhibition of HIF-1αexpression.
机译:在这里,我们报告说,大黄素对鼻咽癌(NPC)细胞的放射增敏作用需要细胞氧化还原状态的调节。我们通过在体外使用NPC细胞和在体内使用异种移植物来评估大黄素的放射敏感性增强能力。进行克隆形成测定以评估NPC细胞存活并确定剂量修饰因子。进行了流式细胞仪,蛋白质印迹分析和体内辐射诱导的肿瘤再生延迟试验,以鉴定大黄素的作用。将CNE-1 NPC细胞暴露于大黄素可增强其放射敏感性。在低氧条件下,HIF-1α的表达显着增加,但单独用大黄素治疗后并没有改变。大黄素下调HIF-1α的mRNA和蛋白表达。暴露于辐射和大黄素的细胞在G2 / M期经历了明显的细胞周期停滞。暴露于大黄素和低氧辐射组的凋亡细胞百分比和活性氧(ROS)水平显着高于其他组。与仅暴露于放射线的CNE-1异种移植物相比,暴露于大黄素的CNE-1异种移植物显示出明显增强的放射作用。我们的数据表明,大黄素在体外和体内均可有效增强CNE-1细胞的放射敏感性。该机制似乎涉及ROS的产生和ROS介导的对HIF-1α表达的抑制。

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