钱 东, 郭艺航, 曾宪亮, 王欢欢, 吴志强, 孟茂斌, 王 平, 袁智勇. 同源重组相关蛋白XRCC3 对食管鳞癌细胞放疗敏感性的影响及其分子机制研究*[J]. 中国肿瘤临床, 2015, 42(1): 37-42. DOI: 10.3969/j.issn.1000-8179.20141557
引用本文: 钱 东, 郭艺航, 曾宪亮, 王欢欢, 吴志强, 孟茂斌, 王 平, 袁智勇. 同源重组相关蛋白XRCC3 对食管鳞癌细胞放疗敏感性的影响及其分子机制研究*[J]. 中国肿瘤临床, 2015, 42(1): 37-42. DOI: 10.3969/j.issn.1000-8179.20141557
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Dong QIAN, Yihang GUO, Xianliang ZENG, Huanhuan WANG, Zhiqiang WU, Maobin MENG, Ping WANG, Zhiyong YUAN. Effects and underlying mechanisms of homologous recombination-associated protein XRCC 3 on esophageal squamous-cell carcinoma radiotherapy response[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2015, 42(1): 37-42. DOI: 10.3969/j.issn.1000-8179.20141557
Citation: Dong QIAN, Yihang GUO, Xianliang ZENG, Huanhuan WANG, Zhiqiang WU, Maobin MENG, Ping WANG, Zhiyong YUAN. Effects and underlying mechanisms of homologous recombination-associated protein XRCC 3 on esophageal squamous-cell carcinoma radiotherapy response[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2015, 42(1): 37-42. DOI: 10.3969/j.issn.1000-8179.20141557
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同源重组相关蛋白XRCC3 对食管鳞癌细胞放疗敏感性的影响及其分子机制研究*

Effects and underlying mechanisms of homologous recombination-associated protein XRCC 3 on esophageal squamous-cell carcinoma radiotherapy response

    摘要
  • 摘要: 目的：探讨同源重组相关蛋白XRCC3 对食管鳞癌（esophage alsqumaouscellcarcinoma ，ESCC）细胞放疗敏感性的影响及其潜在的分子机制。方法：利用免疫印迹（Western blot），逆转录聚合酶链式反应（reverse transcription PCR，RT-PCR）及免疫组织化学（immunohistochemistry ，IHC ）分别检测食管鳞癌细胞以及患者石蜡封存组织标本中XRCC3 的表达；利用慢病毒感染的方式构建稳定沉默XRCC3 表达的食管鳞癌细胞株；运用流式细胞仪通过AnnexinV-PI 双染检测细胞凋亡；免疫荧光染色法检测细胞DNA损伤以及端粒损伤水平的变化。结果：与正常食管鳞状上皮细胞或组织相比，XRCC3 在食管鳞癌细胞及组织中呈高表达；流式及相关实验揭示沉默XRCC3 的表达会增加食管鳞癌细胞在放疗的作用下DNA损伤以及端粒损伤的发生并提高了细胞凋亡的发生比例。结论：XRCC3 通过保护端粒的稳定减少了电离辐射所致的细胞DNA损伤以及细胞凋亡，最终导致食管鳞癌细胞对放疗的相对抵抗，靶向XRCC3 可能成为提高食管鳞癌细胞放疗敏感性的有效策略。

     

    Abstract: Objective:To investigate the effects and underlying mechanisms of XRCC 3 on esophageal squamous-cell carcinoma (ESCC) radiotherapy response. Methods:Expression levels of XRCC3 were detected by reverse transcription PCR, Western blot, and immunohistochemistry. We knocked down XRCC3 with lentiviral infection in ESCC cells. Cell apoptosis was examined by flow cytom-etry. DNA damage and telomere dysfunction-induced foci were determined by immunofluorescence. Results: The expression levels of XRCC 3 in ESCC cells and tissues were higher than those in normal esophageal epithelial cells and corresponding adjacent noncancer -ous esophageal tissues. Knockdown of XRCC 3 in ESCC cells substantially increased the therapeutic efficacy of radiation. We demon -strated that the radiation resistance of XRCC 3 was attributed to the XRCC3-maintaining telomere stability, which reduced ESCC cell death through radiation-induced apoptosis. Conclusion:Our data suggested that XRCC3 protects ESCC cells from ionizing radia -tion -induced DNA damage and death by enhancing telomere stability. Thus, XRCC3 can be used as a promising therapeutic target for ESCCs.

     

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