Zhao Yu,Zhang Junling,Han Xiaodan,et al.FOXO4 D-retro-inverso peptide increases radiosensitivity of non-small cell lung cancer cells[J].Chinese Journal of Radiological Medicine and Protection,2019,39(12):881-886
FOXO4 D-retro-inverso peptide increases radiosensitivity of non-small cell lung cancer cells
Received:September 10, 2019  
DOI:10.3760/cma.j.issn.0254-5098.2019.12.001
KeyWords:Cell apoptosis  Radiosensitivity  FOXO4-DRI  Lung cancer  Cell proliferation
FundProject:国家自然科学基金重点项目(81730086);国家自然科学基金面上项目(81572969)
Author NameAffiliationE-mail
Zhao Yu Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Peking Union Medical College and Chinese Academy of Medical Science, Tianjin 300192, China  
Zhang Junling Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Peking Union Medical College and Chinese Academy of Medical Science, Tianjin 300192, China  
Han Xiaodan Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Peking Union Medical College and Chinese Academy of Medical Science, Tianjin 300192, China  
Fan Saijun Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Peking Union Medical College and Chinese Academy of Medical Science, Tianjin 300192, China fansaijun@irm-cams.ac.cn 
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Abstract::
      Objective To explore the effects of FOXO4 D-retro-inverso peptide (FOXO4-DRI) on the radiosensitivity of non-small cell lung cancer (NSCLC) cells. Methods To detect the effect of FOXO4-DRI on NSCLC cells, H460 and A549 human lung cancer cells were divided into four groups, including untreated control, FOXO4-DRI, γ-ray irradiation and FOXO4-DRI + γ-ray groups. A sigle dose rate of 0.99 Gy γ-rays was used for radiation. H460 cells were administered with 6 μmol/L FOXO4-DRI and A549 cells were adiminstered with 30 μmol/L FOXO4-DRI at 10 min before radiation. Cell viability and survival were detected by CCK-8 assay and colony formation assay, respectively. Cell migration was detected by wound healing assay. Apoptosis and cell cycle arrest were detected with flow cytometry. Results FOXO4-DRI inhibited growth of H460 and A549 cells (t=1.06-50.75, P<0.05), and decreased cell mobility (t=33.37-139.10,P<0.05) and colony formation (t=5.20-93.48,P<0.05). FOXO4-DRI also increased apoptosis (t=2.95-42.00, P<0.05) and caused a cell cycle arrest at G0/G1 phase accompanied with a decreased proportion of G2/M phase (t=3.50-31.59, P<0.05). Furthermore, FOXO4-DRI increased radiosensitivity of both H460 cells and A549 cells (t=2.94-23.40, P<0.05), caused a Further Decrease of radiation-mediated mobility (t=5.25, 7.56,P<0.05) and colony formation (t=8.43-34.00,P<0.05) and a more increase of radiation-induced apoptosis (t=9.20-11.52, P<0.05). FOXO4-DRI also further decreased the proportion of G2/M phase cells but increased the proportion of S phase cells (t=3.85-17.62, P<0.05). Conclusion FOXO4-DRI increases radiosensitivity of NSCLC cells by inducing apoptosis and suppressing cell proliferation.
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