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低表达Nrf2增敏奥沙利铂抗H460细胞增殖作用 被引量：5

Down-regulation of Nrf2 enhances the cytotoxicity of Oxaliplatin to H460 cells
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摘要 目的:建立Nrf2低表达的H460细胞株,可增敏奥沙利铂对肿瘤细胞的抗增殖作用,同时为Nrf2-ARE信号通路的研究提供便捷途径。方法:H460细胞转染pRS-hNrf2后经过筛选得到多个单克隆细胞株,通过Western blotting和GSH含量的检测方法分析各细胞株中Nrf2及其调控基因的表达以及GSH含量的变化,用MTS法检测细胞株对抗癌药物的敏感性。结果:H460细胞转染pRS-hNrf2后筛选建立Nrf2低表达的稳定细胞株H460-C9和H460-C13,与对照组相比其GSH含量均有显著降低(PC9=0.00249,PC13=0.03944);同时,MTS检测表明,抗癌药物奥沙利铂和阿霉素的抗细胞增殖作用在H460-C9和H460-C13细胞株中明显增强。结论:成功建立Nrf2低表达的H460-C9和H460-C13细胞株,与对照组细胞株相比,低表达Nrf2可增敏奥沙利铂对肿瘤细胞的抗增殖作用。 Objective： To establish a stable H460 cell line with Nrf2 down-regulation to study the role of Nrf2 in Oxaliplatin resistance.Methods： Nrf2 down-regulated H460 cell line was obtained by transfecting cells with pRS-hNrf2 and followed by screening for Nrf2 expression by Western blotting.The cell lines were further characterized by analysing cellular GSH levels and cytotoxicity to anti-cancer drugs with MTS.Results： Nrf2 down-regulated H460 cell lines were established successfully.Cellular GSH level reduced significantly in the H460-C9 and H460-C13 compared to control cells（PC9= 0.00249,PC13= 0.03944）.Down-regulation of Nrf2 in H460 sensitized the anti-cancer effect of Oxaliplatin and Doxorubicin.Conclusion： Nrf2 plays an important role in drug resistance.Down regulation of Nrf2 in H460 cell enhances cytotoxicity of Oxaliplatin.
作者 辛爱 任环宇 唐修文
机构地区 浙江大学医学院生物化学与遗传学系
出处 《浙江大学学报（医学版）》 CAS CSCD 北大核心 2010年第1期11-16,共6页 Journal of Zhejiang University(Medical Sciences)
基金 国家自然科学基金(30973555) 卫生部/浙江省卫生厅(WKJ2007-2-008) 浙江省科技厅(2008C23054)
关键词 核胞浆转运蛋白类 氧化性应激 基因表达 反应元件 有机铂化合物 抗药性 肿瘤 谷胱甘肽 肺肿瘤 Karyopherins Oxidative stress Gene expression Response elements Organoplatinum compounds Drug resistance neoplasm Glutathione Lung neoplasms
分类号 R73-3 [医药卫生—肿瘤]
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参考文献12

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同被引文献59

  • 1王红军,廖新华,崔飞博,魏光兵.siRNA阻断NF-κB信号通路抑制胃癌SGC-7901细胞的增殖及侵袭[J].西安交通大学学报（医学版）,2012,33(4):466-469. 被引量：3
  • 2张晔,田昕,刘云鹏,曲秀娟,杨向红,侯科佐,滕月娥,张敬东.蟾蜍灵对顺铂耐药胃癌SGC7901细胞增殖与凋亡的影响及其作用机制[J].西安交通大学学报（医学版）,2012,33(4):498-500. 被引量：14
  • 3杨晓云,李延青,袁俊华,郭玉婷,张燕,朱强.利用RNA i技术抑制结肠癌NRF2基因表达[J].基础医学与临床,2006,26(10):1072-1077. 被引量：4
  • 4MINERVA R G, KWAK M K, DOLAN P M, et al. Sensitivity to carcinogenesis is increased and chemoprotective efficacy of enzyme inducers is lost in nrf2 transcription factor-deficient mice [ J ]. PNAS ,2001,98 (6) :3410-3415.
  • 5MORIMITSU Y, NAKAGAWA Y, HAYASHI K, et al. A sulforaphane analogue that potently activates the Nrf2-dependent detoxification pathway [ J ]. J Biol Chem,2002,277 (5) : 3456-3463.
  • 6LEE J M, CALKINS M J, CHAN K, et al. Identification of the NF-E2-related factor-2- dependent genes conferring protection against oxidative stress in primary cortical astrocytes using oligonucleotide microarray analysis [ J ]. J Biol Chem,2003,278 (14) : 12029-12038.
  • 7THIMMULAPPA R K, MAI K H, SRISUMA S, et al. Identification of Nrf2-regulated genes induced by the chemopreventive agent sulforaphane by oligonucleotide microarray [ J ]. Cancer Res, 2002, 62(18) :5196-5203.
  • 8SHIBATA T, OHTA T, TONG K I, et al. Cancer related mutations in NRF2 impair its recognition by Keapl-Cul3 E3 ligaseand promote malignancy [J].PNAS,2008,105 (36) : 13568-13573.
  • 9DINKOVA-KOSTOVA A T, HOLTZCLAW W D, COLE R N, et al. Direct evidence that sulfhydryl groups of Keapl are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants [ J]. PNAS, 2002,99 ( 18 ) : 11908- 11913.
  • 10LEE J S, SURH Y J. Nrf2 as a novel molecular target for chemoprevention [ J ]. Cancer Lett, 2005,224 (2):171-184.

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浙江大学学报（医学版）
2010年 第1期

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