Radiosensitization of NSCLC cells to X-rays and carbon ions by the CHK1/CHK2 inhibitor AZD7762, Honokiol and Tunicamycin
- PDF / 5,321,073 Bytes
- 10 Pages / 595.276 x 790.866 pts Page_size
- 63 Downloads / 126 Views
ORIGINAL ARTICLE
Radiosensitization of NSCLC cells to X‑rays and carbon ions by the CHK1/CHK2 inhibitor AZD7762, Honokiol and Tunicamycin Bingtao Liu1,2,3,4 · Weiqiang Chen1,2,3,4 · Hongbin Li1,2,3,4 · Feifei Li1,2,3,4 · Xiaodong Jin1,2,3,4 · Qiang Li1,2,3,4 Received: 18 August 2019 / Accepted: 13 August 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract 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. Keywords Radiosensitivity · X-rays · Carbon ions · AZD7762 · Honokiol · Tunicamycin
Introduction Lung cancer is one of the most prevalent malignancies around the world. In China, the morbidity and mortality due to lung cancer ranked first among all the tumors, which occupied 20% and 27% of the total cancer cases, respectively (Zheng et al. 2015). Lung cancer was classified into two categories according to the histopathological typing: small-cell * Xiaodong Jin [email protected] * Qiang Li [email protected] 1
Institute of Modern Physics, Chinese Academy of Sciences, 509 Nanchang Road, Lanzhou 730000, Gansu, China
2
Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China
3
Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Lanzhou 730000, Gansu, China
4
University of Chinese Academy of Sciences, Beijing 100049, China
lung cancer (SCLC, 20%) and non-small-cell lung cancer (NSCLC) which accounts for more than 80 ~ 85% of all lung tumors. Approximately 35% of patients with NSCLC are presented with locally advanced non metastatic disease (Auperin et al. 2010). Radiochemotherapy is an essential module of the multimodal treatment of locally advanced NSCLC patients. Despite significant progress of radiotherapy delivery (Schwart
Data Loading...
