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双泛素蛋白诱导自噬对肝癌细胞放射敏感度的影响

周亭芳, 邱波, 唐晶, 张淑芳, 谭丽梅, 欧阳威

周亭芳, 邱波, 唐晶, 张淑芳, 谭丽梅, 欧阳威. 双泛素蛋白诱导自噬对肝癌细胞放射敏感度的影响[J]. 肿瘤防治研究, 2015, 42(11): 1081-1085. DOI: 10.3971/j.issn.1000-8578.2015.11.005
引用本文: 周亭芳, 邱波, 唐晶, 张淑芳, 谭丽梅, 欧阳威. 双泛素蛋白诱导自噬对肝癌细胞放射敏感度的影响[J]. 肿瘤防治研究, 2015, 42(11): 1081-1085. DOI: 10.3971/j.issn.1000-8578.2015.11.005
ZHOU Tingfang, QIU Bo, TANG Jing, ZHANG Shufang, TAN Limei, OUYANG Wei. FAT10-induced Autophagy Regulates Radiosensitivity of Hepatocellular Carcinoma Cells[J]. Cancer Research on Prevention and Treatment, 2015, 42(11): 1081-1085. DOI: 10.3971/j.issn.1000-8578.2015.11.005
Citation: ZHOU Tingfang, QIU Bo, TANG Jing, ZHANG Shufang, TAN Limei, OUYANG Wei. FAT10-induced Autophagy Regulates Radiosensitivity of Hepatocellular Carcinoma Cells[J]. Cancer Research on Prevention and Treatment, 2015, 42(11): 1081-1085. DOI: 10.3971/j.issn.1000-8578.2015.11.005

双泛素蛋白诱导自噬对肝癌细胞放射敏感度的影响

详细信息
    作者简介:

    周亭芳(1972-),女,硕士,副主任医师,从事肿瘤放化疗工作

  • 中图分类号: R735.7

FAT10-induced Autophagy Regulates Radiosensitivity of Hepatocellular Carcinoma Cells

  • 摘要: 目的 探讨双泛素蛋白(FAT10)对肝癌细胞自噬水平的调节作用,并进一步明确FAT10诱导自噬对肝癌细胞放射敏感度的影响。方法 本实验首先通过Western blot及免疫组织化学方法分别从肝癌细胞及临床标本中验证FAT10对自噬相关蛋白的调控作用,进而通过克隆存活实验以明确FAT10诱导自噬对肝癌细胞放射敏感度的调节作用。结果 FAT10过表达可促进自噬相关蛋白Beclin1和LC3-Ⅰ/Ⅱ表达并抑制p62的表达,且经X射线照射后上述表达改变更明显。免疫组织化学分析结果显示FAT10与Beclin1具有显著相关性(P<0.01),高表达FAT10的肝癌标本同时伴有Beclin1表达升高。克隆存活实验表明FAT10过表达增加肝癌细胞的放射抵抗性,敲除FAT10则增加肝癌细胞的放射敏感度。当使用自噬抑制剂3-MA或特异性干扰Beclin1以抑制肝癌细胞发生自噬后则上述FAT10表达改变不能引起肝癌细胞的放射敏感度的改变。结论 FAT10表达增加可通过诱导自噬形成进而增强肝癌细胞的放射抵抗性。

     

    Abstract: Objective To investigate the effect of FAT10 regulating autophagy in hepatocellular carcinoma (HCC) cells and determine the function of autophagy in the radiosensitivity of HCC cells. Methods The regulating effect of FAT10 on autophagy-related proteins in HCC cells and clinical specimens were detected by Western blot and immunohistochemistry (IHC). Clonogenic assay was employed to observe the changes of radiosensitivity in HCC cells under a regulation of autophagy. Results Elevated FAT10 expression was associated with significant increase of autophagy-related proteins Beclin1and LC3-Ⅰ/Ⅱ and decrease of p62 proteins in HCC cells, especially when underwent an X-ray irradiation. A significant correlation between FAT10 and Beclin1 expression was further conformed by IHC analysis from 35 HCC specimens (P<0.01), and FAT10 overexpression was mostly accompanied by elevated Beclin1 expression. Furthermore, the increased expression of FAT10 was associated with dramatical radiation resistance, and knockdown of FAT10 displayed significantly radiosensitivity. However, when treated with 3-MA, a cell-permeable autophagic sequestration blocker, or specifical knockdown of Beclin1, there was no obvious changes in the radiosensitivity of HCC cells when FAT10 expression was changed. Conclusion Overexpression of FAT10 is associated with an enhancement of autophagy and enhances the radiosensitivity of HCC cells.

     

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出版历程
  • 收稿日期:  2014-12-08
  • 修回日期:  2015-05-04
  • 刊出日期:  2015-11-24

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