XRCC3 is a promising target to improve the radiotherapy effect of esophageal squamous cell carcinoma.
XRCC3 is a promising target to improve the radiotherapy effect of esophageal squamous cell carcinoma.
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XRCC3是提高食管鳞癌放疗效果的一个有前景的靶点
DOI：
10.1111/cas.12820
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发表时间：
2015-12
期刊：
影响因子：
5.7
通讯作者：
Qian D
中科院分区：
文献类型：
--
作者：
Cheng J;Liu W;Zeng X;Zhang B;Guo Y;Qiu M;Jiang C;Wang H;Wu Z;Meng M;Zhuang H;Zhao L;Hao J;Cai Q;Xie D;Pang Q;Wang P;Yuan Z;Qian D
放射治疗广泛应用于食管鳞状细胞癌的治疗。Rad 51相关蛋白XRCC 3在DNA双链断裂的重组修复中发挥作用，以维持染色体稳定性和修复DNA损伤。本研究旨在探讨XRCC 3对食管鳞癌放射敏感性的影响及其机制。XRCC 3在ESCC细胞和组织中的表达高于正常食管上皮细胞和相应癌旁食管组织。XRCC 3高表达与ESCC对放化疗的抵抗呈正相关，是ESCC患者疾病特异性生存期短的独立预测因子。此外，通过敲低ESCC细胞中的XRCC 3，体外和体内放射治疗的疗效显著增加。XRCC 3在两种XRCC 3沉默的ESCC细胞中的异位过表达显著增强了ESCC细胞对放射治疗的抵抗力。此外，XRCC 3赋予的辐射抗性归因于同源重组的增强、端粒稳定性的维持以及辐射诱导的细胞凋亡和有丝分裂灾难导致的ESCC细胞死亡的减少。我们的数据表明，XRCC 3通过促进DNA损伤修复和/或增强端粒稳定性来保护ESCC细胞免受电离辐射诱导的死亡。XRCC 3可能是一个新的放射敏感性预测因子和有希望的治疗ESCC的靶点。
Radiotherapy is widely applied for treatment of esophageal squamous cell carcinoma (ESCC). The Rad51‐related protein XRCC3 plays roles in the recombinational repair of DNA double‐strand breaks to maintain chromosome stability and repair DNA damage. The present study aimed to investigate the effect of XRCC3 on the radiotherapy response of ESCC and the underlying mechanisms of the roles of XRCC3 in ESCC radiosensitivity. XRCC3 expression in ESCC cells and tissues was higher than that in normal esophageal epithelial cells and corresponding adjacent noncancerous esophageal tissue. High XRCC3 expression was positively correlated with resistance to chemoradiotherapy in ESCC and an independent predictor for short disease‐specific survival of ESCC patients. Furthermore, the therapeutic efficacy of radiotherapy in vitro and in vivo was substantially increased by knockdown of XRCC3 in ESCC cells. Ectopic overexpression of XRCC3 in both XRCC3‐silenced ESCC cells dramatically enhanced ESCC cells' resistance to radiotherapy. Moreover, radiation resistance conferred by XRCC3 was attributed to enhancement of homologous recombination, maintenance of telomere stability, and a reduction of ESCC cell death by radiation‐induced apoptosis and mitotic catastrophe. Our data suggest that XRCC3 protects ESCC cells from ionizing radiation‐induced death by promoting DNA damage repair and/or enhancing telomere stability. XRCC3 may be a novel radiosensitivity predictor and promising therapeutic target for ESCC.