Silencing Ku80 using small interfering RNA enhanced radiation sensitivity in vitro and in vivo.
Silencing Ku80 using small interfering RNA enhanced radiation sensitivity in vitro and in vivo.
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DOI：
10.3892/ijo.30.6.1477
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发表时间：
2007-06
影响因子：
5.2
通讯作者：
Y. Nimura;T. Kawata;K. Uzawa;Junko Okamura;Cuihua Liu;M. Saito;H. Shimada;N. Seki;A. Nakagawara;Hisao Ito;T. Ochiai;H. Tanzawa
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文献类型：
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作者：
Y. Nimura;T. Kawata;K. Uzawa;Junko Okamura;Cuihua Liu;M. Saito;H. Shimada;N. Seki;A. Nakagawara;Hisao Ito;T. Ochiai;H. Tanzawa
Ku 80是DNA双链断裂修复的重要组成部分，Ku 80缺陷导致对电离辐射的极端敏感性。我们研究了放射治疗结合小干扰RNA沉默Ku 80是否能增强体外和体内的放射敏感性。用包含在日本血凝病毒包膜载体中的Ku 80 siRNA转染7个人癌细胞系。将H1299细胞植入用Ku 80 siRNA和辐射处理的雄性BALB/C nu/nu裸鼠中。经2-戈伊照射后，转染Ku 80 siRNA的细胞株存活率较未转染的细胞株下降10%~ 26%.与未用siRNA处理的组相比，Ku 80 siRNA联合处理后0.5 h在A549细胞中和6 h在H1299细胞中的γ-H2 AX磷酸化阳性率显著更高（分别为77.6%，p=0.033和76.7%，p=0.026）。与单独放射相比，用联合疗法治疗的H1299异种移植肿瘤体积减小并且重新生长缓慢。我们的研究结果表明，Ku 80 siRNA和辐射组成的联合治疗有助于抑制肿瘤生长，可能是一种新的癌症治疗策略。
Ku80 is an important component of DNA double-strand break repair, and Ku80 deficiency leads to extreme sensitivity to ionizing radiation. We studied whether radiation therapy combined with Ku80 silencing by small interfering RNA enhances radiation sensitivity in vitro and in vivo. Seven human cancer cell lines were transfected with Ku80 siRNA included in hemagglutinating virus of Japan envelope vector. H1299 cells were implanted into male BALB/C nu/nu nude mice treated with Ku80 siRNA and irradiation. The survival rate of cell lines transfected with Ku80 siRNA decreased by 10% to 26% with 2-Gy irradiation compared with untransfected cell lines. The gamma-H2AX phosphorylation-positive rates of Ku80 siRNA combined treatment 0.5 h after irradiation in A549 cells and 6 h in H1299 cells were significantly higher (77.6%, p=0.033 and 76.7%, p=0.026, respectively), compared with the groups not treated with siRNA. H1299 xenograft tumors treated with combined therapy decreased in volume and re-grew slowly compared with radiation alone. Our results indicate that combined therapy consisting of Ku80 siRNA and irradiation contributes to inhibition of tumor growth and may be a novel strategy for cancer treatment.