Radiosensitization by Inhibiting Survivin in Human Hepatoma HepG2 Cells to High-LET Radiation
Radiosensitization by Inhibiting Survivin in Human Hepatoma HepG2 Cells to High-LET Radiation
复制标题
抑制人肝癌 HepG2 细胞中 Survivin 对高 LET 辐射的放射增敏作用
DOI：
10.1269/jrr.10134
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发表时间：
2011-05-01
影响因子：
2
通讯作者：
Dai, Zhongying
中科院分区：
文献类型：
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作者：
Jin, Xiaodong;Li, Qiang;Dai, Zhongying
在这项研究中，生存素是否在介导高LET辐射抗性的人肝癌细胞中发挥直接作用进行了调查。设计了针对生存素mRNA的小干扰RNA（siRNA），并转染人肝癌HepG 2细胞。Real-time PCR和Western blotting分析显示，Survivin特异性siRNA处理后，HepG 2细胞中Survivin的表达在转录和转录后水平均下降。半胱天冬酶-3活性也用酶标仪测定。暴露于高LET碳离子后，与未用siRNA处理的细胞相比，在用siRNA处理的细胞中观察到降低的克隆形成存活效应、增加的凋亡率和半胱天冬酶-3活性。转染生存素特异性siRNA的细胞也增加了G（2）/M阻滞的水平。这些结果表明，Survivin在HepG 2细胞对高LET辐射的耐受性中起一定的介导作用，抑制Survivin的表达可能有助于提高重离子对放射耐受性实体瘤的治疗效果。
In this study, whether survivin plays a direct role in mediating high-LET radiation resistance in human hepatoma cells was investigated. Small interfering RNA (siRNA) targeting survivin mRNA was designed and transfected into human hepatoma HepG2 cells. Real-time PCR and western blotting analyses revealed that survivin expression in HepG2 cells decreased at both transcriptional and post-transcriptional levels after treatment with survivin-specific siRNA. Caspase-3 activity was determined with a microplate reader assay as well. Following exposure to high-LET carbon ions, a reduced clonogenic survival effect, increased apoptotic rates and caspase-3 activity were observed in the cells treated with the siRNA compared to those untreated with the siRNA. The cells with transfection of the survivin-specific siRNA also increased the level of G(2)/M arrest. These results suggest that survivin definitely plays a role in mediating the resistance of HepG2 cells to high-LET radiation and depressing survivin expression might be useful to improve the therapeutic efficacy of heavy ions for radioresistant solid tumors.