赵玉,张俊伶,韩晓丹,等.FOXO4-DRI多肽增加非小细胞肺癌细胞放射敏感性研究[J].中华放射医学与防护杂志,2019,39(12):881-886.Zhao Yu,Zhang Junling,Han Xiaodan,et al.FOXO4 D-retro-inverso peptide increases radiosensitivity of non-small cell lung cancer cells[J].Chin J Radiol Med Prot,2019,39(12):881-886
FOXO4-DRI多肽增加非小细胞肺癌细胞放射敏感性研究
FOXO4 D-retro-inverso peptide increases radiosensitivity of non-small cell lung cancer cells
投稿时间:2019-09-10  
DOI:10.3760/cma.j.issn.0254-5098.2019.12.001
中文关键词:  细胞凋亡  放射敏感性  FOXO4-DRI  肺癌  细胞增殖
英文关键词:Cell apoptosis  Radiosensitivity  FOXO4-DRI  Lung cancer  Cell proliferation
基金项目: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)
作者单位E-mail
赵玉 中国医学科学院北京协和医学院放射医学研究所 天津市放射医学与分子核医学重点实验室 300192  
张俊伶 中国医学科学院北京协和医学院放射医学研究所 天津市放射医学与分子核医学重点实验室 300192  
韩晓丹 中国医学科学院北京协和医学院放射医学研究所 天津市放射医学与分子核医学重点实验室 300192  
樊赛军 中国医学科学院北京协和医学院放射医学研究所 天津市放射医学与分子核医学重点实验室 300192 fansaijun@irm-cams.ac.cn 
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中文摘要:
      目的 探讨FOXO4-DRI多肽对非小细胞肺癌(NSCLC)细胞放射敏感性的影响。方法 为检测FOXO4-DRI对NSCLC细胞的影响,将H460和A549细胞按照射与给药方式分为对照组、FOXO4-DRI组、单纯照射组、照射+FOXO4-DRI组。采用剂量率为0.99 Gy/min γ射线单次照射,在照射前10 min对H460细胞给予FOXO4-DRI 6 μmol/L,A549细胞给予FOXO4-DRI 30 μmol/L。采用CCK-8法检测照射后24、48和72 h细胞存活率;用结晶紫染色法检测细胞克隆形成数目;用伤口愈合实验检测细胞迁移程度;用流式细胞术检测细胞凋亡和细胞周期的改变。结果 与对照组相比,FOXO4-DRI组H460细胞和A549细胞存活率降低(t=1.06~50.75,P<0.05)、迁移率降低(t=33.37~139.10,P<0.05),克隆形成数目减少(t=5.20~93.48,P<0.05)。FOXO4-DRI诱导了细胞凋亡(t=2.95~42.00,P<0.05),导致G0/G1细胞周期阻滞以及G2/M期细胞比例下降(t=3.50~31.59,P<0.05)。与照射组相比,FOXO4-DRI可进一步降低辐照后的细胞存活率(t=2.94~23.40,P<0.05),减少辐照后克隆形成数目(t=8.43~34.00,P<0.05)和细胞迁移率(t=5.25、7.56,P<0.05),增加细胞凋亡(t=9.20~11.52,P<0.05)。照射+FOXO4-DRI组细胞,G2/M期细胞比例进一步下降,S期细胞增加(t=3.85~17.62,P<0.05)。结论 FOXO4-DRI多肽通过促进细胞凋亡,降低细胞增殖能力和迁移率,可以提高NSCLC细胞放射敏感性。
英文摘要:
      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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