Survivin expressions in human hepatoma HepG2 cells exposed to ionizing radiation of different LET
Survivin expressions in human hepatoma HepG2 cells exposed to ionizing radiation of different LET
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DOI：
10.1007/s00411-008-0165-0
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发表时间：
2008-07-01
影响因子：
1.7
通讯作者：
Li, Qiang
中科院分区：
文献类型：
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作者：
Jin, Xiao-dong;Gong, Li;Li, Qiang
Survivin是凋亡抑制蛋白（IAP）家族的成员，其干扰包括半胱天冬酶激活的线粒体后事件。为研究不同线性能量转移（LET）照射对Survivin表达的影响，采用X射线和碳离子照射体外培养的人肝癌HepG 2细胞。细胞的敏感性低和高LET辐射的菌落形成。RT-PCR和Western blot分别检测Survivin在mRNA和蛋白水平的表达。流式细胞仪检测辐射诱导的细胞周期阻滞和凋亡。我们发现，低LET X射线诱导生存素表达的剂量依赖性增加。高LET碳离子照射后，存活素的表达从0 ~ 4戈伊逐渐增加，6戈伊后下降。与0 ~ 4戈伊的X射线相比，碳离子照射后，Survivin表达更明显，G（2）/M期阻滞更强。这些观察结果表明，有一个不同的生存素表达响应于不同的LET辐射和周期阻滞机制可能与之有关。此外，我们的数据诱导细胞凋亡的假设是一致的，低LET X射线辐射诱导的生存素表达可能在抑制细胞凋亡中发挥关键作用。然而，在用离子照射后，存活素的抗凋亡功能不明显，可能是因为密集电离辐射产生的严重损伤。
Survivin is a member of the inhibitors of apoptosis (IAP) protein family that interferes with post-mitochondrial events including activation of caspases. To examine the regulation of survivin expression in response to irradiation with different linear energy transfer (LET), human hepatoma HepG2 cells were irradiated in vitro with X-rays and carbon ions. Cellular sensitivities to low- and high-LET radiation were determined by colony formation. Survivin expression at mRNA and protein level were measured with RT-PCR and Western blot analyses, respectively. Radiation-induced cell cycle arrest and apoptosis were investigated with flow cytometry. We found that low-LET X-rays induced dose-dependent increases in survivin expression. After exposure to high-LET carbon ions, survivin expression gradually increased from 0 to 4 Gy, and then declined at 6 Gy. More pronounced survivin expression, stronger G(2)/M phase arrest was observed after exposure to carbon ions in comparison with X-rays at doses from 0 to 4 Gy. These observations indicate that there is a differential survivin expression in response to different LET radiations and the cycle arrest mechanism may be associated with it. In addition, our data on induction of apoptosis are compatible with the assumption that survivin expression induced by low-LET X-rays radiation may play a critical role in inhibiting apoptosis. However, after irradiation with ions, an anti-apoptotic function of survivin is not evident, possibly because of the serious damage produced by densely ionizing radiation.