A chemical inhibitor of p53 that protects mice from the side effects of cancer therapy
A chemical inhibitor of p53 that protects mice from the side effects of cancer therapy
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DOI：
10.1126/science.285.5434.1733
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发表时间：
1999-09-10
期刊：
影响因子：
56.9
通讯作者：
Gudkov, AV
中科院分区：
文献类型：
--
作者：
Komarov, PG;Komarova, EA;Gudkov, AV
癌症的化疗和放射治疗往往有严重的副作用，限制了它们的疗效。由于这些效应在一定程度上是由P53介导的细胞凋亡决定的，暂时抑制P53被认为是在治疗P53缺陷的肿瘤过程中防止正常组织损伤的一种治疗策略。为了测试这种可能性，我们分离了一种小分子，用于可逆地阻断依赖于P53的转录激活和细胞凋亡。这种化合物，匹氟菊酯-α，在不促进肿瘤形成的情况下，保护小鼠免受与抗癌治疗相关的致命的基因毒性应激。因此，P53的抑制剂可能是减少癌症治疗的副作用和与P53诱导相关的其他类型的应激反应的有用残渣。
Chemotherapy and radiation therapy for cancer often have severe side effects that limit their efficacy. Because these effects are in part determined by p53-mediated apoptosis, temporary suppression of p53 has been suggested as a therapeutic strategy to prevent damage of normal tissues during treatment of p53-deficient tumors. To test this possibility, a small molecule was isolated for its ability to reversibly block p53-dependent transcriptional activation and apoptosis. This compound, pifithrin-alpha, protected mice from the Lethal genotoxic stress associated with anticancer treatment without promoting the formation of tumors. Thus, inhibitors of p53 may be useful dregs for reducing the side effects of cancer therapy and other types of stress associated with p53 induction.