Targeting RAD51 enhances chemosensitivity of adult T-cell leukemia-lymphoma cells by reducing DNA double-strand break repair
Targeting RAD51 enhances chemosensitivity of adult T-cell leukemia-lymphoma cells by reducing DNA double-strand break repair
复制标题
靶向 RAD51 通过减少 DNA 双链断裂修复来增强成人 T 细胞白血病-淋巴瘤细胞的化疗敏感性
DOI：
10.3892/or.2019.7384
复制
发表时间：
2019-10
期刊：
影响因子：
4.2
通讯作者：
Liang Aibin
中科院分区：
文献类型：
--
作者：
Yang Meng;Tian Xiaoxue;Fan Zhuoyi;Yu Wenlei;Li Zheng;Zhou Jie;Zhang Wenjun;Liang Aibin
RAD 51是一种重要的同源重组蛋白，具有修复DNA损伤、维持基因多样性和稳定性的作用。已有研究表明，RAD 51的过表达与肿瘤细胞对化疗的耐药性有关，而DNA损伤修复（DDR）系统活性的增强有助于成人T细胞白血病-淋巴瘤（ATL）对化疗的耐药性。因此，靶向RAD 51是通过诱导DNA损伤使ATL细胞对化疗药物敏感的潜在策略。一般来说，细胞可以通过DDR修复轻微的DNA损伤;然而，严重的DNA损伤可能会导致细胞毒性，无法恢复。目前，通过shRNA和伊马替尼下调RAD 51，通过降低同源重组（HR）的活性使Jurkat细胞对依托泊苷敏感。我们发现，通过shRNA抑制RAD 51抑制肿瘤细胞的增殖，并促进依托泊苷处理后的Jurkat细胞的凋亡。重要的是，伊马替尼下调RAD 51明显增加了依托泊苷处理后Jurkat细胞的凋亡。这些结果表明，RAD 51可能作为成人T细胞白血病-淋巴瘤（ATL）临床治疗的新靶点，并可能提高白血病患者的生存率。
RAD51, is a key homologous recombination protein that repairs DNA damage and maintains gene diversity and stability. Previous studies have demonstrated that the over-expression of RAD51 is associated with chemotherapy resistance of tumor cells to chemotherapy, and enhanced activity of DNA damage repair (DDR) systems contributes to resistance of adult T-cell leukemia-lymphoma (ATL) resistance to chemotherapy. Thus, targeting RAD51 is a potential strategy for the sensitization of ATL cells to chemotherapeutic drugs by inducing DNA damage. In general, cells can repair minor DNA damage through DDR; however, serious DNA damage may cause cell toxicity in cells which cannot be restored. In the present, down regulation of RAD51 by shRNA and imatinib sensitized Jurkat cells to etoposide by decreasing the activity of homologous recombination (HR). We found that the suppression of RAD51 by shRNA inhibited tumor cells proliferation and enhanced apoptosis of Jurkat cells after etoposide treatment. Importantly, downregulation of RAD51 by imatinib obviously increased the apoptosis of Jurkat cell after etoposide treatment. These results demonstrated that RAD51 may be of great value to as a novel target for the clinical treatment of adult T-cell leukemia-lymphoma (ATL), and it may improve the survival of leukemia patients.
登录
查看更多内容
影响因子：
--
作者：
Wiegmans AP;Al-Ejeh F;Chee N;Yap PY;Gorski JJ;Da Silva L;Bolderson E;Chenevix-Trench G;Anderson R;Simpson PT;Lakhani SR;Khanna KK
通讯作者：
Khanna KK
DOI：
10.1038/nrc2607
发表时间：
2009-05
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
DOI：
--
发表时间：
1999
期刊：
--
影响因子：
--
作者：
J. Masters;B. Palsson
通讯作者：
J. Masters;B. Palsson
DOI：
10.1074/jbc.273.7.3799
发表时间：
1998-02
期刊：
The Journal of Biological Chemistry
影响因子：
--
作者：
Zhi-Min Yuan;Yinyin Huang;T. Ishiko;S. Nakada;T. Utsugisawa;S. Kharbanda;Rong Wang;P. Sung;A. Shinohara;R. Weichselbaum;D. Kufe
通讯作者：
Zhi-Min Yuan;Yinyin Huang;T. Ishiko;S. Nakada;T. Utsugisawa;S. Kharbanda;Rong Wang;P. Sung;A. Shinohara;R. Weichselbaum;D. Kufe
影响因子：
2.9
作者：
Li, Yang;He, Yujiong;Luo, Yu
通讯作者：
Luo, Yu