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Targeted inhibition of acidic nucleoplasmic DNA-binding protein 1 enhances radiosensitivity of non-small cell lung cancer
Cancer Letters ( IF 9.1 ) Pub Date : 2022-01-20 , DOI: 10.1016/j.canlet.2022.01.020
Wenfeng Gou 1 , Xiaojun Yu 2 , Shaohua Wu 1 , Hongying Wu 1 , Huajie Chang 1 , Leyuan Chen 1 , Huiqiang Wei 1 , Changfen Bi 1 , Hongxin Ning 1 , Yingliang Wu 2 , Wenbin Hou 1 , Daiying Zuo 2 , Yiliang Li 1
Affiliation  

Acidic nucleoplasmic DNA binding protein 1 (AND-1, also known as WD repeat and HMG-box DNA-binding protein 1, WDHD1) plays an important role in DNA replication and repair, but the relationship between AND-1 and radiosensitivity is not well understood. This research explored the impact of AND-1 on the radiosensitivity of non-small cell lung cancer (NSCLC) for the first time. NSCLC cells were treated with AND-1 siRNA or a new AND-1 inhibitor, CH-3, and clonogenic survival assay was used to characterize cell radiosensitivity. Cell cycle and apoptosis were examined by flow cytometry. DNA damage was detected by comet assay, immunofluorescence, and homologous recombination (HR) repair assay. Finally, the radiosensitization effect of CH-3 was investigated in vivo in a xenograft tumor model. The results showed that AND-1 inhibition significantly increased the radiosensitivity of NSCLC cells. Mechanistically, AND-1 inhibitor (CH-3) induced G2/M phase arrest by regulating the ATM signaling pathway and enhanced irradiation-induced DNA damage by inhibiting the DNA HR repair pathway. CH-3 enhanced the radiosensitivity of NSCLC cells in vivo. The development of radiosensitizers that target AND-1 may provide an alternative strategy to inhibit NSCLC.



中文翻译:

靶向抑制酸性核质DNA结合蛋白1可增强非小细胞肺癌的放射敏感性

酸性核质DNA结合蛋白1(AND-1,又称WD重复和HMG-box DNA结合蛋白1,WDHD1)在DNA复制和修复中起重要作用,但AND-1与放射敏感性的关系并不好明白了。本研究首次探讨了AND-1对非小细胞肺癌(NSCLC)放射敏感性的影响。用 AND-1 siRNA 或新的 AND-1 抑制剂 CH-3 处理 NSCLC 细胞,并使用克隆形成存活试验来表征细胞放射敏感性。通过流式细胞术检查细胞周期和细胞凋亡。通过彗星试验、免疫荧光和同源重组 (HR) 修复试验检测 DNA 损伤。最后,在体内研究了 CH-3 的放射增敏作用。在异种移植肿瘤模型中。结果表明,AND-1抑制显着增加了NSCLC细胞的放射敏感性。从机制上讲,AND-1 抑制剂 (CH-3) 通过调节 ATM 信号通路诱导 G2/M 期阻滞,并通过抑制 DNA HR 修复通路增强辐射诱导的 DNA 损伤。CH-3 增强了体内NSCLC 细胞的放射敏感性。靶向 AND-1 的放射增敏剂的开发可能提供抑制 NSCLC 的替代策略。

更新日期:2022-01-30
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