Although radiotherapy, especially carbon-ion radiotherapy, is an effective treatment modality against non-small-cell lung cancer (NSCLC), studies using radiation combined with sensitizer for improving the efficacy of radiotherapy are still needed. In this work, we aimed to investigate in NSCLC A549 and H1299 cell lines the effects of different linear energy transfer (LET) radiations combined with diverse sensitizing compounds. Cells pretreated with the CHK1/CHK2 inhibitor AZD7762, Honokiol or Tunicamycin were irradiated with low-LET X-rays and high-LET carbon ions. Cell survival was assessed using the clonogenic cell survival assay. Cell cycle distribution and apoptosis were measured with flow cytometry, and DNA double strand break (DSB) and repair were detected using γ-H2AX immunofluorescence staining. Our results revealed that AZD7762, Honokiol and Tunicamycin demonstrated low cytotoxicity to NSCLC cells and a pronounced radiosensitizing effect on NSCLC cells exposed to carbon ions than X-rays. Unrepaired DNA DSB damages, the abrogation of G2/M arrest induced by irradiation, and finally apoptotic cell death were the main causes of the radiosensitizing effect. Thus, our data suggest that high-LET carbon ion combined with these compounds may be a potentially effective therapeutic strategy for locally advanced NSCLC.

尽管放射疗法，尤其是碳离子放射疗法是针对非小细胞肺癌（NSCLC）的有效治疗方式，但仍需要结合放射线与敏化剂联合使用以提高放射疗法疗效的研究。在这项工作中，我们旨在研究NSCLC A549和H1299细胞系中不同线性能量转移（LET）辐射与各种敏化化合物的结合作用。用低LET X射线和高LET碳离子辐照用CHK1 / CHK2抑制剂AZD7762，厚朴酚或丘尼霉素预处理的细胞。使用克隆形成细胞存活测定法评估细胞存活。用流式细胞仪检测细胞周期分布和凋亡，并用γ-H2AX免疫荧光染色检测DNA双链断裂（DSB）和修复。我们的结果表明，AZD7762 厚朴酚和衣霉素对NSCLC细胞显示出低细胞毒性，并且比X射线对暴露于碳离子的NSCLC细胞具有明显的放射增敏作用。辐射致敏作用的主要原因是未修复的DNA DSB损伤，辐射诱导的G2 / M抑制的废除，最后凋亡的细胞死亡。因此，我们的数据表明，与这些化合物结合的高LET碳离子可能是局部晚期NSCLC的潜在有效治疗策略。