LGK-974对人肝癌细胞系HepG2的辐射增敏作用

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LGK-974对人肝癌细胞系HepG2的辐射增敏作用

辐射生物学与医学 | 更新时间：2021-12-10

- LGK-974对人肝癌细胞系HepG2的辐射增敏作用
- Effect of LGK-974 in enhancing the radiosensitivity of HepG2 hepatoma cells
- 辐射研究与辐射工艺学报 2016年34卷第6期
- 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：
  
  [ "田丹, 女, 1989年8月出生, 2013年毕业于华侨大学化工学院, 现为北京协和医学院在读研究生", "TIAN Dan (female) was born in August 1989, and graduated from the College of Chemical Engineering of Huaqiao University in 2013. Now she is a master candidate in Peking Union Medical College" ]
  樊飞跃, 博士, 研究员, E-mail:Faithyfan@hotmail.com Ph.D. FAN Feiyue, professor, E-mail:Faithyfan@hotmail.com
- 基金信息：
  
  国家自然科学基金(31200634);国家自然科学基金(31300695);天津市科学技术普及项目(15KPXM01SF056);中国医学科学院、北京协和医学院“中央级公益性科研院所基本科研经费”(2016ZX310068);中国医学科学院放射医学研究所创新团队基金(1605)
- DOI：10.11889/j.1000-3436.2016.rrj.34.060203
  中图分类号：
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田丹, 王彦, 王芹, 等. LGK-974对人肝癌细胞系HepG2的辐射增敏作用[J]. 辐射研究与辐射工艺学报, 2016,34(6):060203-9.

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, 2016,34(6):060203-9.
田丹, 王彦, 王芹, 等. LGK-974对人肝癌细胞系HepG2的辐射增敏作用[J]. 辐射研究与辐射工艺学报, 2016,34(6):060203-9. DOI： 10.11889/j.1000-3436.2016.rrj.34.060203.

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, 2016,34(6):060203-9. 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

references

W Chen , R Zheng , P D Baade , 等 . Cancer statistics in China, 2015 . CA-A Cancer Journal for Clinicians , 2016 . 66 (2 ):115 -132 . DOI:10.3322/caac.21338http://doi.org/10.3322/caac.21338 .

N Fukumitsu , T Okumura , H Ishikawa , 等 . Liver cancer: progress in diagnosis and treatments. Topics: VI. Progress in treatments of liver cancer; 7. Radiotherapy of liver cancer . Nihon Naika Gakkai Zasshi , 2014 . 103 (1 ):116 -122 . DOI:10.2169/naika.103.116http://doi.org/10.2169/naika.103.116.

X Liu , X Zhang , Y Ding , 等 . Nuclear factor E2-related factor-2 (Nrf2) negatively regulates NLRP3 inflammasome activity by inhibiting reactive oxygen species (ROS)-induced NLRP3 priming . Antioxidants & Redox Signaling , 2016 . 1 (3 ):89 -102 . DOI:10.1089/ars.2015.6615http://doi.org/10.1089/ars.2015.6615 .

N K Zenkov , E B Menshchikova , V O Tkachev . Keap1/Nrf2/ARE redox-sensitive signaling system as a pharmacological target . Biochemistry-Moscow , 2013 . 78 (1 ):19 -36 . DOI:10.1134/S0006297913010033http://doi.org/10.1134/S0006297913010033 .

S Kabaria , D C Choi , A D Chaudhuri , 等 . MicroRNA-7 activates Nrf2 pathway by targeting Keap1 expression . Free Radical Biology and Medicine , 2015 . 89 548 -556 . DOI:10.1016/j.freeradbiomed.2015.09.010http://doi.org/10.1016/j.freeradbiomed.2015.09.010 .

E Bhakkiyalakshmi , D Sireesh , P Rajaguru , 等 . The emerging role of redox-sensitive Nrf2-Keap1 pathway in diabetes . Pharmacological Research , 2015 . 91 104 -114 . DOI:10.1016/j.phrs.2014.10.004http://doi.org/10.1016/j.phrs.2014.10.004 .

M Liu , XD Yao , W Li , 等 . Nrf2 sensitizes prostate cancer cells to radiation via decreasing basal ROS levels . Biofactors , 2015 . 41 (1 ):52 -57 . DOI:10.1002/biof.1200http://doi.org/10.1002/biof.1200 .

Y Yamashita , T Ueyama , T Nishi , 等 . Nrf2-inducing anti-oxidation stress response in the rat liver-new beneficial effect of lansoprazole . PLoS One , 2014 . 9 (5 ):e97419 DOI:10.1371/journal.pone.0097419http://doi.org/10.1371/journal.pone.0097419 .

S Jayakumar , A Kunwar , S K Sandur , 等 . Differential response of DU145 and PC3 prostate cancer cells to ionizing radiation: role of reactive oxygen species, GSH and Nrf2 in radiosensitivity . Biochimica et Biophysica Acta-molecular Cell Research , 2014 . 1840 (1 ):485 -494 . DOI:10.1016/j.bbagen.2013.10.006http://doi.org/10.1016/j.bbagen.2013.10.006 .

J T Morgan , V K Raghunathan , Y R Chang , 等 . Wnt inhibition induces persistent increases in intrinsic stiffness of human trabecular meshwork cells . Experimental Eye Research , 2015 . 132 174 -178 . DOI:10.1016/j.exer.2015.01.025http://doi.org/10.1016/j.exer.2015.01.025 .

J C Nault , S Rebouissou , R J Zucman . NRF2/KEAP1 and Wnt/beta-catenin in the multistep process of liver carcinogenesis in humans and rats . Hepatology , 2015 . 62 (3 ):677 -679 . DOI:10.1002/hep.27828http://doi.org/10.1002/hep.27828 .

P Rada , A I Rojo , A Offergeld , 等 . Wnt-3A regulates an Axin1/NRF2 complex that regulates antioxidant metabolism in hepatocytes . Antioxid Redox Signal , 2015 . 22 (7 ):555 -571 . DOI:10.1089/ars.2014.6040http://doi.org/10.1089/ars.2014.6040 .

J Y Choi , H J Cho , S G Hwang , 等 . Podophyllotoxin acetate enhances gamma-ionizing radiation-induced apoptotic cell death by stimulating the ROS/p38/caspase pathway . Biomedicine & Pharmacotherapy , 2015 . 70 111 -118 . DOI:10.1016/j.biopha.2014.12.038http://doi.org/10.1016/j.biopha.2014.12.038 .

A O Fontana , M A Augsburger , N Grosse , 等 . Differential DNA repair pathway choice in cancer cells after proton-and photon-irradiation . Radiotherapy and Oncology , 2015 . 116 (3 ):374 -380 . DOI:10.1016/j.radonc.2015.08.014http://doi.org/10.1016/j.radonc.2015.08.014 .

S Zhou , W Ye , Q Shao , 等 . Nrf2 is a potential therapeutic target in radioresistance in human cancer . Critical Reviews in Oncology Hematology , 2013 . 88 (3 ):706 -715 . DOI:10.1016/j.critrevonc.2013.09.001http://doi.org/10.1016/j.critrevonc.2013.09.001 .

M C Lu , J A Ji , Y L Jiang , 等 . An inhibitor of the Keap1-Nrf2 protein-protein interaction protects NCM460 colonic cells and alleviates experimental colitis . Scientific Reports , 2016 . 6 265 -285 . DOI:10.1038/srep26585http://doi.org/10.1038/srep26585 .

G Shanmugam , M Narasimhan , R Sakthivel , 等 . A biphasic effect of TNF-alpha in regulation of the Keap1/Nrf2 pathway in cardiomyocytes . Redox Biology , 2016 . 9 77 -89 . DOI:10.1016/j.redox.2016.06.004http://doi.org/10.1016/j.redox.2016.06.004 .

N Kawai , R Kuraishi , H Kaneko . Wnt, Frizzled, and sFRP gene expression patterns during gastrulation in the starfish Patiria (Asterina) pectinifera . Gene Expression Patterns , 2016 . 21 (1 ):19 -27 . DOI:10.1016/j.gep.2016.06.003http://doi.org/10.1016/j.gep.2016.06.003 .

Y Yang , M Mlodzik . Wnt-Frizzled/planar cell polarity signaling: cellular orientation by facing the wind (Wnt) . Annual Review of Cell and Developmental Biology , 2015 . 31 623 -646 . DOI:10.1146/annurev-cellbio-100814-125315http://doi.org/10.1146/annurev-cellbio-100814-125315 .

J Liu , S Pan , M H Hsieh , 等 . Targeting Wnt-driven cancer through the inhibition of Porcupine by LGK-974 . Proceedings of the National Academy of Sciences of the United States of America , 2013 . 110 (50 ):20224 -20229 . DOI:10.1073/pnas.1314239110http://doi.org/10.1073/pnas.1314239110 .

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北京协和医学院中国医学科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

北京协和医学院&中国医学科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天津

中国科学院生物物理研究所

北京医科大学药学院

（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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