A survivin-associated adaptive response in radiation therapy.
A survivin-associated adaptive response in radiation therapy.
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DOI：
10.1158/0008-5472.can-12-4640
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发表时间：
2013-07-15
期刊：
影响因子：
11.2
通讯作者：
Weichselbaum RR
中科院分区：
文献类型：
--
作者：
Grdina DJ;Murley JS;Miller RC;Mauceri HJ;Sutton HG;Li JJ;Woloschak GE;Weichselbaum RR
极低剂量的电离辐射可以在细胞中诱导适应性反应，从而增强对更大暴露的抵抗力。细胞凋亡抑制剂 (IAP) 蛋白生存素与许多细胞应激的适应性反应有关。图像引导放射治疗中使用的计算机轴向断层扫描 (CAT) 用来定位和监测肿瘤反应，使用的辐射剂量非常低，范围为 0.5 至 100 mGy。我们研究了这些非常低的辐射剂量以及间隔 24 小时的两次 2 Gy 剂量（标准的传统放射治疗剂量方案）启动适应性反应的能力，从而导致暴露细胞的辐射抵抗力升高。人结肠癌 (RKO36)、小鼠肉瘤 (SA-NH) 以及转化的小鼠胚胎成纤维细胞 (MEF)、野生型 (WT) 或缺乏功能性肿瘤坏死因子受体 1 和 2 (TNFR1−R2−) 的细胞用于评估它们在体外生长至汇合或作为 C57BL/6 侧翼肿瘤时表达适应性反应的相对能力 老鼠。与未接受 100 mGy 或更低剂量的细胞相比，这些细胞的存活率提高了 5% 至 20% (P ≤ 0.05)。此外，暴露于 100 mGy 的细胞表现出生存素水平升高、细胞凋亡频率降低以及如果用生存素 siRNA 转染则丧失适应性反应。如果在整个图像引导放射治疗过程中定期诱导这种生存素介导的适应性反应，则有可能影响结果。
Adaptive responses can be induced in cells by very low doses of ionizing radiation resulting in an enhanced resistance to much larger exposures. The inhibitor of apoptosis (IAP) protein, survivin, has been implicated in many adaptive responses to cellular stress. Computerized axial tomography (CAT) used in image guided radiotherapy to position and monitor tumor response utilizes very low radiation doses ranging from 0.5 to 100 mGy. We investigated the ability of these very low radiation doses administered along with two 2 Gy doses separated by 24 h, a standard conventional radiotherapy dosing schedule, to initiate adaptive responses resulting in the elevation of radiation resistance in exposed cells. Human colon carcinoma (RKO36), mouse sarcoma (SA-NH), along with transformed mouse embryo fibroblasts (MEF), wild type (WT) or cells lacking functional tumor necrosis factor receptors 1 and 2 (TNFR1−R2−) were used to assess their relative ability to express an adaptive response when grown either to confluence in vitro or as tumors in the flank of C57BL/6 mice. The survival of each of these cells was elevated from 5 to 20% (P ≤ 0.05) as compared to cells not receiving a 100 mGy or lesser dose. Additionally, the cells exposed to 100 mGy exhibited elevations in survivin levels, reductions in apoptosis frequencies, and loss of an adaptive response if transfected with survivin siRNA. This survivin-mediated adaptive response has the potential for affecting outcomes if regularly induced throughout a course of image guided radiation therapy.