Radiation abscopal antitumor effect is mediated through p53.
Radiation abscopal antitumor effect is mediated through p53.
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DOI：
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发表时间：
2003-04
期刊：
影响因子：
11.2
通讯作者：
K. Camphausen;M. Moses;C. Ménard;M. Sproull;W. Beecken;J. Folkman;M. O’Reilly
中科院分区：
文献类型：
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作者：
K. Camphausen;M. Moses;C. Ménard;M. Sproull;W. Beecken;J. Folkman;M. O’Reilly
观察到，对身体的局部区域进行放射治疗，对远离辐射部位的肿瘤具有抗肿瘤作用，这被称为“非内窥镜效应”。为了了解这一不寻常现象的机制，我们检查了这种效应是否通过P53介导，P53是一种在受辐射细胞中上调的蛋白质复合体。对C57BL/6(野生型P53)和P53基因缺失的B6.129S2-TrP53(Tm1Tyj)小鼠的非荷瘤小腿进行照射，观察其对Lewis肺癌(LLC)和纤维肉瘤T241(纤维肉瘤)的远景效应。在携带野生型p53的小鼠中，与假照射动物相比，移植到中线背部的LLC和T241肿瘤在腿部受到5次10-Gy射线照射时的生长速度明显放缓，这表明这种异常效应不是肿瘤特异性的。当腿部的放射剂量减少(12次，每次2Gy.)，对LLC肿瘤生长的抑制作用减弱，表明放射剂量依赖于非局部性效应。相反，当p53基因缺失的动物或野生型p53小鼠的腿部接受照射(5次10Gy次)时，肿瘤生长并未延迟。这些数据表明，P53是辐射诱导的非局域效应的关键媒介，并表明P53下游的通路在引发这种反应中是重要的。
The observation that radiation treatment to a local area of the body results in an antitumor effect for tumors distant to the radiation site has been termed the "abscopal effect." To understand the mechanism of this unusual phenomenon, we examined whether the effect was mediated through p53, a protein complex up-regulated in irradiated cells. Non-tumor-bearing legs of C57BL/6 (wild-type p53) and p53 null B6.129S2-Trp53(tm1Tyj) mice were irradiated to determine whether an abscopal effect could be observed against Lewis lung carcinoma (LLC) and T241 (fibrosarcoma) implanted at a distant site. In mice with wild-type p53, both LLC and T241 tumors implanted into the midline dorsum grew at a significantly slower rate when the leg of the animal was exposed to five 10-Gy fractions of radiation compared with sham-irradiated animals, suggesting that the abscopal effect is not tumor specific. When the radiation dose to the leg was reduced (twelve fractions of 2 Gy each), the inhibition of LLC tumor growth was decreased indicating a radiation-dose dependency for the abscopal effect. In contrast, when the legs of p53 null animals or wild-type p53 mice treated with pifithrin-alpha (a p53 blocker) were irradiated (five 10-Gy fractions), tumor growth was not delayed. These data implicate p53 as a key mediator of the radiation-induced abscopal effect and suggest that pathways downstream of p53 are important in eliciting this response.