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首页> 外文期刊>Biochemistry and Cell Biology >Inhibiting polo-like kinase 1 enhances radiosensitization via modulating DNA repair proteins in non-small-cell lung cancer
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Inhibiting polo-like kinase 1 enhances radiosensitization via modulating DNA repair proteins in non-small-cell lung cancer

机译：抑制马酚样激酶1通过调节非小细胞肺癌中的DNA修复蛋白增强辐射敏化。

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摘要

To assure faithful chromosome segregation, cells make use of the spindle assembly checkpoint, which can be activated in aneuploid cancer cells. In this study, the efficacies of inhibiting polo-like kinase 1 (PLK1) on the radiosensitization of non-small-cell lung cancer (NSCLC) cells were studied. Clonogenic survival assay was performed to identify the effects of the PLK1 inhibitor on radiosensitivity within NSCLC cells. Mitotic catastrophe assessment was used to measure the cell death and histone H2AX protein (gamma H2AX) foci were utilized to assess the DNA double-strand breaks (DSB). The transcriptome was analyzed via unbiased profiling of microarray expression. The results showed that the postradiation mitotic catastrophe induction and the DSB repair were induced by PLK1 inhibitor BI-6727, leading to an increase in the radiosensitivity of NSCLC cells. BI-6727 in combination with radiation significantly induced the delayed tumor growth. PLK1-silenced NSCLC cells showed an altered mRNA and protein expression related to DNA damaging, replication, and repairing, including the DNA-dependent protein kinase (DNAPK) and topoisomerase II alpha (TOPO2A). Furthermore, inhibition of PLK1 blocked 2 important DNA repair pathways. To summarize, our study showed PLK1 kinase as an option in the therapy of NSCLC.
机译：为了确保忠实的染色体隔离，细胞利用主轴组件检查点，其可以在非植物癌细胞中被激活。在该研究中，研究了抑制马酚样激酶1（PLK1）对非小细胞肺癌（NSCLC）细胞的放射敏化的疗效。进行克隆基存活测定以鉴定PLK1抑制剂对NSCLC细胞内放射敏感性的影响。使用有丝分裂灾难评估来测量用于测量细胞死亡和组蛋白H2AX蛋白（γH2AX）焦点，用于评估DNA双链断裂（DSB）。通过微阵列表达的无偏析分析分析转录组。结果表明，PLK1抑制剂BI-6727诱导了缓解有丝分裂灾难诱导和DSB修复，导致NSCLC细胞的放射敏感性增加。 Bi-6727与辐射结合显着诱导延迟肿瘤生长。 PLK1沉默的NSCLC细胞显示出改变的mRNA和蛋白质表达与DNA损伤，复制和修复有关，包括DNA依赖性蛋白激酶（DNAPK）和拓扑异构酶IIα（TOPO2A）。此外，PLK1的抑制阻断了2个重要的DNA修复途径。总而言之，我们的研究显示PLK1激酶作为NSCLC治疗中的选择。

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