Survivin, a target to modulate the radiosensitivity of Ewing's sarcoma
Survivin, a target to modulate the radiosensitivity of Ewing's sarcoma
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DOI：
10.1007/s00066-012-0223-z
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发表时间：
2012-11-01
影响因子：
3.1
通讯作者：
Eich, H. T.
中科院分区：
文献类型：
--
作者：
Greve, B.;Sheikh-Mounessi, F.;Eich, H. T.
放射治疗是尤文肉瘤多模式治疗的重要组成部分。与其他肉瘤相比，尤文肿瘤通常对放射治疗有良好的反应。然而，始终有肿瘤具有放射抵抗的表型，其潜在的机制尚不清楚。本研究旨在探讨Survivin蛋白表达与尤文肉瘤放射敏感性的关系。采用基于siRNA的基因敲除方法，研究Survivin蛋白表达对4种尤文肉瘤细胞株在照射前后细胞增殖、双链断裂(DSB)诱导和修复、细胞凋亡和集落形成能力的影响。由于Survivin基因敲除，STA-ET-1细胞表现出细胞增殖减少，辐射诱导的双链断裂数量增加，修复减少。单纯基因敲除可增加细胞凋亡率，联合照射可进一步增加细胞凋亡率。Survivin基因敲除联合放射治疗可显著减少克隆形成。Survivin是尤文肉瘤中的一种辐射诱导蛋白，其下调使细胞对辐射敏感。Survivin基因敲除联合放射治疗显著抑制细胞的增殖、修复和集落形成，并且比单独单独治疗更能增加细胞的凋亡率。这可能为尤文氏肉瘤的放射治疗开辟新的视角。
Radiotherapy constitutes an essential element in the multimodal therapy of Ewing's sarcoma. Compared to other sarcomas, Ewing tumors normally show a good response to radiotherapy. However, there are consistently tumors with a radioresistant phenotype, and the underlying mechanisms are not known in detail. Here we investigated the association between survivin protein expression and the radiosensitivity of Ewing's sarcoma in vitro.An siRNA-based knockdown approach was used to investigate the influence of survivin expression on cell proliferation, double-strand break (DSB) induction and repair, apoptosis and colony-forming ability in four Ewing's sarcoma cell lines with and without irradiation.Survivin protein and mRNA were upregulated in all cell lines tested in a dose-dependent manner. As a result of survivin knockdown, STA-ET-1 cells showed reduced cell proliferation, an increased number of radiation-induced DSBs, and reduced repair. Apoptosis was increased by knockdown alone and increased further in combination with irradiation. Colony formation was significantly reduced by survivin knockdown in combination with irradiation.Survivin is a radiation-inducible protein in Ewing's sarcoma and its down-regulation sensitizes cells toward irradiation. Survivin knockdown in combination with radiation inhibits cell proliferation, repair, and colony formation significantly and increases apoptosis more than each single treatment alone. This might open new perspectives in the radiation treatment of Ewing's sarcoma.