Antisense inhibition of ATM gene enhances the radiosensitivity of head and neck squamous cell carcinoma in mice.
Antisense inhibition of ATM gene enhances the radiosensitivity of head and neck squamous cell carcinoma in mice.
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ATM基因反义抑制增强小鼠头颈鳞状细胞癌放射敏感性
DOI：
10.1186/1756-9966-27-56
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发表时间：
2008-10-26
期刊：
影响因子：
--
通讯作者：
Liu S
中科院分区：
文献类型：
--
作者：
Zou J;Qiao X;Ye H;Yang Y;Zheng X;Zhao H;Liu S
头颈部鳞状细胞癌（HNSCC）放射治疗后的治疗失败可能是一个重要的问题。本研究旨在通过反义寡核苷酸（AS-ODNs）抑制ATM mRNA表达，在体外和体内对SCCVII细胞进行放射增敏，并探讨其可能的放射增敏机制。采用实时荧光定量PCR和Western blotting方法分别检测细胞ATM mRNA和蛋白表达的变化。克隆形成存活实验检测照射后SCCVII细胞的存活能力，流式细胞仪检测细胞周期和凋亡情况。结果ATMAS-ODNs处理的SCCVII细胞中ATMAmRNA和蛋白的相对表达量分别为未处理细胞的25.7 ± 3.1%和24.1 ± 2.8%（P< 0.05）;照射后，ATMAS-ODNs处理组的细胞存活分数（SF）低于其他组（P< 0.05），G2/M期细胞比例减少，凋亡率增加（P< 0.05）。X线照射对SCCVII细胞实体瘤生长的抑制率为23.2 ± 2.7%，联合ATMAS-ODNs照射组为56.1 ± 3.8%，差异有显著性（P< 0.05）。ATMAS-ODNs联合照射组细胞凋亡指数为19.6 ± 3.2，显著高于其他组（P< 0.05）。结论抑制ATM表达可使SCCVII细胞对电离辐射敏感。其机制可能是G2/M期细胞周期检查点控制缺陷和辐射诱导凋亡增强。
BackgroundTreatment failure after radiotherapy of head and neck squamous cell carcinoma (HNSCC) could be a significant problem. Our objective is to sensitize SCCVII cells to ionizing radiationin vitroandin vivothrough inhibiting ATM expression using antisense oligodeoxynucleotides (AS-ODNs), and investigate the potential mechanism of radiosensitization.MethodsWe designed and synthesized AS-ODNs that target ATM mRNA to reduce the ATM expression. The influence on the expression of ATM mRNA and protein in SCCVII cells were analysed by real-time quantitative PCR and western blotting respectively. Clonogenic survival assay was performed to detect the survival ability of SCCVII cells after irradiation, while flow cytometry used to analyse the cell cycle and apoptosis. The volume of solid tumors generated with SCCVII cells was measured, and cell apoptosis was analysed by TUNEL assay after irradiation.ResultsThe relative ATM mRNA and protein expression in SCCVII cells treated with ATM AS-ODNs were decreased to 25.7 ± 3.1% and 24.1 ± 2.8% of that in untreated cells respectively (P< 0.05). After irradiation, the survival fraction (SF) of cells treated with ATM AS-ODNs was lower than that of other groups at the same dose of radiation (P< 0.05), while the percentage of cells in G2/M phase decreased and apoptotic rate of cells increased(P< 0.05). The inhibition rate in SCCVII cells solid tumor exposed to X-ray alone was 23.2 ± 2.7%, while it was 56.1 ± 3.8% in the group which irradiated in combination with the treatment of ATM AS-ODNs (P< 0.05). The apoptotic index for the group irradiated in combination with ATM AS-ODNs injection was 19.6 ± 3.2, which was significantly higher than that of others (P< 0.05)ConclusionInhibition of ATM expression sensitized SCCVII cells to ionizing radiationin vitroandin vivo. The potential mechanism should be the defective G2/M cell cycle checkpoint control and enhanced radiation-induced apoptosis.
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DOI：
10.1007/s00432-007-0278-x
发表时间：
2008-02-01
影响因子：
3.6
作者：
Gaul, Leander;Mandl-Weber, Sonja;Schmidmaier, Ralf
通讯作者：
Schmidmaier, Ralf
影响因子：
11.2
作者：
Peng, YL;Woods, RG;Bedford, JS
通讯作者：
Bedford, JS
影响因子：
21.3
作者：
Shiloh, Y;Lehmann, AR
通讯作者：
Lehmann, AR
DOI：
10.1002/hed.1130
发表时间：
2001-10-01
影响因子：
2.9
作者：
Khurana, D;Martin, EA;Strome, SE
通讯作者：
Strome, SE
影响因子：
8.8
作者：
Dunne, A L;Price, M E;Mothersill, C;McKeown, S R;Robson, T;Hirst, D G
通讯作者：
Hirst, D G