Contribution of Decreased Expression of Ku70 to Enhanced Radiosensitivity by Sodium Butyrate in Glioblastoma Cell Line (U251)
Contribution of Decreased Expression of Ku70 to Enhanced Radiosensitivity by Sodium Butyrate in Glioblastoma Cell Line (U251)
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DOI：
10.1007/s11596-011-0381-8
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发表时间：
2011-06-01
影响因子：
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通讯作者：
Wu, Gang
中科院分区：
文献类型：
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作者：
Li, Yuhui;Zhou, Hongxia;Wu, Gang
本研究探讨了丁酸钠(NAB)对U-251细胞的放射增敏作用及其可能机制。克隆细胞存活实验检测U251细胞对放射的增敏作用。用RT-PCR和Western blotting分别检测Ku70mRNA和蛋白的表达。分别于电离辐射后不同时间点及与NaB联合照射后测量γ-H_2AX焦点。结果表明，与单纯照射相比，联合治疗后细胞存活率显著降低，D0和DQ值均降低(D0：1.43Gyvs.1.76Gy.DQ：1.22Gyvs.2.05Gy.)，增敏比(SER)达1.23。联合用药后不同时间点的细胞平均伽马-H_2AX病灶数显著增加，且NAB呈剂量依赖性抑制Ku70mRNA和蛋白的表达。结论：NAB诱导的放射敏感性增强与Ku70的表达抑制和γ-H_2AX焦点的增加有关，表明DSB修复能力降低。
The present study investigated the enhanced radiosensitivity of U-251 cells induced by sodium butyrate (NaB) and its possible mechanisms. Increased radiosensitivity of U251 cells was examined by clonogenic cell survival assays. The expression of Ku70 mRNA and protein was detected by using RT-PCR and Western blotting respectively. gamma-H2AX foci were measured at different time points after ionizing irradiation alone or combined with NaB treatment. The results showed that cell survival rate was significantly reduced, both D0 and Dq values were decreased (D0: 1.43 Gy vs. 1.76 Gy; Dq: 1.22 Gy vs. 2.05 Gy) after the combined treatment as compared with irradiation alone, and sensitivity enhancing ratio (SER) reached 1.23. The average number of gamma-H2AX foci per cell receiving the combined treatment was significantly increased at different time points, and the expression levels of Ku70 mRNA and protein were suppressed by NaB in a dose-dependent manner. It was concluded that enhanced radiosensitivity induced by NaB involves an inhibited expression of Ku70 and an increase in gamma-H2AX foci, which suggests decreased ability in DSB repair.