Effect of LGK-974 in enhancing the radiosensitivity of HepG2 hepatoma cells

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Effect of LGK-974 in enhancing the radiosensitivity of HepG2 hepatoma cells

Radiobiology and Radiomedicine | 更新时间：2021-12-10

- Effect of LGK-974 in enhancing the radiosensitivity of HepG2 hepatoma cells
- Journal of Radiation Research and Radiation Processing Vol. 34, Issue 6, (2016)
- 作者机构：
  
  1.北京协和医学院中国医学科学院放射医学研究所天津 300192
  2.北京协和医学院比较动物中心中国医学科学院医学实验动物研究所北京 100021
- 作者简介：
- 基金信息：
  
  the National Natural Science Foundation of China(31200634);the National Natural Science Foundation of China(31300695);Tianjin science and technology popularization project(15KPXM01SF056);Fundamental Research Funds for CAMS & PUMC(2016ZX310068);Research Funds for the Inno-vation Team of IRM-CAMS(1605)
- DOI：10.11889/j.1000-3436.2016.rrj.34.060203
  CLC：
扫描看全文
Dan TIAN, Yan WANG, Qin WANG, et al. Effect of LGK-974 in enhancing the radiosensitivity of HepG2 hepatoma cells. [J]. Journal of Radiation Research and Radiation Processing 34(6):060203-9(2016)
DOI：

Dan TIAN, Yan WANG, Qin WANG, et al. Effect of LGK-974 in enhancing the radiosensitivity of HepG2 hepatoma cells. [J]. Journal of Radiation Research and Radiation Processing 34(6):060203-9(2016) DOI： 10.11889/j.1000-3436.2016.rrj.34.060203.

摘要

观察LGK-974（CAS：1243244-14-5）对人肝癌细胞系HepG2的辐射增敏作用，并探讨可能的作用机制。应用四甲基偶氮唑盐（MTT）比色法检测LGK-974对HepG2细胞的生长抑制作用；细胞克隆形成法确定1.0 μmol/L LGK-974对HepG2细胞放疗敏感性的影响；H,2,DCFH-DA探针流式细胞法检测细胞活性氧（Reactive oxygen species，ROS）水平；RT-PCR及Western Blot法检测,Nrf2,及其下游,NQO-1,、,HO-1,基因的转录水平和蛋白表达水平。结果显示，LGK-974抑制HepG2细胞的生长分裂和增殖，24、48、72 h的半抑制浓度（IC,50,）为4.3、2.14、0.536 μmol/L（,p,<, 0.05）；1.0 μmol/L LGK-974对HepG2细胞的放射增敏比（,SER,D0,）为1.37；LGK-974能增大辐射产生的ROS水平（,p,<, 0.05）；照射后,Nrf2,及其下游基因,HO-1,、,NQO-1,的转录水平和表达水平均增加；LGK-974能降低辐射对,Nrf2,、,HO-1,和,NQO-1,的转录和表达水平的增加作用（,p,<, 0.05）。由此得出，LGK-974对人肝癌细胞系HepG2具有明显的辐射增敏作用，其机制可能是抑制Nrf2信号通路，阻止细胞缓解辐射产生的氧化压力。

Abstract

To observe the effects of LGK-974 on radiosensitivity of HepG2 cells and explore its possible mechanism, MTT assay was applied to examine the growth inhibition of LGK-974 to HepG2; the radiosensitivity of HepG2 cells treated by 1.0 μmol/L LGK-974 was detected by clone formation assay; the reactive oxygen species level was examined by H,2,DCFH-DA probe flow cytometry method; the mRNA and protein levels of Nrf2, and the downstream gene ,HO-1,NQO-1, were accessed by RT-PCR and Western Blot, respectively. The results showed LGK-974 could inhibit HepG2 cells growth, and the IC,50, of 24 h, 48 h and 72 h were 4.3 μmol/L, 2.14 μmol/L, and 0.536 μmol/L, respectively (,p,<, 0.05); the ,SER,D0, of 1.0 μmol/L LGK-974 was 1.37; LGK-974 could increase the ROS level produced by irradiation (,p,<, 0.05); irradiation could increase the transcription and expression of ,Nrf2,HO-1, and ,NQO-1, and LGK-974 could weaken these effects. The study reveals that LGK-974 can enhance the radiosensitivity of HepG2 cells. The mechanism might inhibit the Nrf2 signaling pathway and prevent cells reducing the oxidative stress produced by irradiation.

关键词

LGK-974HepG2细胞Nrf2活性氧辐射增敏

Keywords

LGK-974HepG2 cellsNrf2Reactive oxygen species (ROS)Radiosensitization

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Related Institution

Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College

Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Peking Union Medical College & Chinese Academy of Medical Science

Institute of Biopysics, Academia Sinica

School of Pharmaceutical Sciences, Beijing Medical University

（北京协和医学院中国医学科学院放射医学研究所）

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