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人肝癌HepG2细胞表达甲胎蛋白抑制AMD3100诱导凋亡的研究

龙儒桃, 翁启芳, 朱明月, 李 伟, 马 兰, 谢协驹, 李孟森

龙儒桃, 翁启芳, 朱明月, 李 伟, 马 兰, 谢协驹, 李孟森. 人肝癌HepG2细胞表达甲胎蛋白抑制AMD3100诱导凋亡的研究[J]. 肿瘤防治研究, 2013, 40(12): 1109-1113. DOI: 10.3971/j.issn.1000-8578.2013.12.001
引用本文: 龙儒桃, 翁启芳, 朱明月, 李 伟, 马 兰, 谢协驹, 李孟森. 人肝癌HepG2细胞表达甲胎蛋白抑制AMD3100诱导凋亡的研究[J]. 肿瘤防治研究, 2013, 40(12): 1109-1113. DOI: 10.3971/j.issn.1000-8578.2013.12.001
LONG Rutao, WENG Qifang, ZHU Mingyue, LI Wei, MA Lan, XIE Xieju. Research of Alpha Fetoprotein Inhibits AMD3100 Induced Apoptosis of Human Haptoma HepG2 Cells[J]. Cancer Research on Prevention and Treatment, 2013, 40(12): 1109-1113. DOI: 10.3971/j.issn.1000-8578.2013.12.001
Citation: LONG Rutao, WENG Qifang, ZHU Mingyue, LI Wei, MA Lan, XIE Xieju. Research of Alpha Fetoprotein Inhibits AMD3100 Induced Apoptosis of Human Haptoma HepG2 Cells[J]. Cancer Research on Prevention and Treatment, 2013, 40(12): 1109-1113. DOI: 10.3971/j.issn.1000-8578.2013.12.001

人肝癌HepG2细胞表达甲胎蛋白抑制AMD3100诱导凋亡的研究

基金项目: 国家自然科学基金资助项目(81360307,81260306,81160261,31060164,30960153);教育部新世纪优秀人才支持计划资助项目(NCET-10-0124);教育部重点科学技术资助项目(211146);海南省重点科技资助项目(DZXM20110038);海南省自然科学基金资助项目(309034, 310044)
详细信息
    作者简介:

    龙儒桃(1979-),女,硕士,讲师,主要从事细胞信号转导的研究

    通讯作者:

    李孟森,E-mail: mengsenli@163.com

  • 中图分类号: R735.7

Research of Alpha Fetoprotein Inhibits AMD3100 Induced Apoptosis of Human Haptoma HepG2 Cells

  • 摘要: 目的 研究CXCR4信号对人肝癌HepG2细胞增殖及甲胎蛋白(alpha fetoprotein, AFP)表达在肝癌细胞耐受诱导凋亡中的作用。方法 MTT 法检测CXCR4信号的拮抗剂AMD3100对人肝癌细胞HepG2增殖的影响,并用Western blot分析AMD3100处理前后AFP、CXCR4的表达变化;用RNA干扰技术抑制AFP表达24 h 后再给予AMD3100处理24 h,荧光显微镜观察HepG2细胞的形态学变化以及流式细胞术分析细胞的凋亡情况。结果 AMD3100对人肝癌HepG2细胞的增殖有明显的抑制作用;AMD3100处理后HepG2细胞的CXCR4和AFP表达明显受到抑制;干扰AFP 表达可协同AMD3100诱导HepG2细胞凋亡。 结论 HepG2细胞通过表达AFP导致癌细胞耐受AMD3100诱导的凋亡。

     

    Abstract: Objective To investigate the role of CXC chemokine receptor 4(CXCR4) signal effects on the expression of alpha fetoprotein(AFP) in human hepatoma cells, HepG2, and effects of AFP on AMD3100 induced apoptosis of HepG2 cells. Methods The effects of AMD3100, an antagonistic agent of CXCR4 ligand, on proliferation of human hepatocellular carcinoma cells HepG2 was detected by MTT. Western blot was applied to identify the expression of AFP and CXCR4. Small interference RNA was used to suppress expression of AFP in HepG2 cells, and apoptosis of HepaG2 cells were analazed by fl uorescent microscopy and fl ow cytometry. Results Here we demonstrated that high concentration (>1.0μg/ml) of AMD3100 might inhibit proliferation of HepG2 cells. AMD3100 had a function to down-regulate the expression of CXCR4 and AFP in HepG2 cells.The results also indicated that the expression of AFP had synergies with AMD3100 in inducing apoptosis of HepG2 cells in vitro. Conclusion HepG2 cells were tolerant to apoptosis induced by AMD3100 through expressing AFP.

     

  • [1] de Martel C, Ferlay J, Franceschi S, et al. Global burden of cancers attributable to infections in 2008: a review and synthetic analysis[J]. Lancet Oncol, 2012,13(6): 607-15.
    [2] Dudich E, Semenkova L, Gorbatova E, et al. Growth-regulative activity of human alpha- fetoprotein for different types of tumor and normal cells[J]. Tumor Biol, 1998,19(1): 30-40.
    [3] Li M, Li H, Li C, et al. Cytoplasmic alpha-fetoprotein functions as a co-repressor in RA-RAR signaling to promote the growth of human hepatoma Bel 7402 cells[J]. Cancer Lett, 2009, 285(2): 19 0-9.
    [4] Wang S, Jiang W, Chen X, et al. Alpha-fetoprotein acts as a novel signal molecule and mediates transcription of Fn14 in human hepatocellular carcinoma[J]. J Hepatol, 2012,57(2): 322-9.
    [5] Balkwill F. The significance of cancer cell expression of the chemokine receptor CXCR4[J]. Semin Cancer Biol, 2004,14(3): 17 1-9.
    [6] Kim SW, Kim HY, Song IC,et al. Cytoplasmic trapping of CXCR4 in hepatocellular carcinoma cell lines[J]. Cancer Res Treat, 20 08,40(2): 53-61.
    [7] Peng SB, Peek V, Zhai Y, et al. Akt activation, but not extracellular signal-regulated kinase activation, is required for SDF-1α/ CXCR4-mediated migration of epitheloid carcinoma cells[J]. Mol Cancer Res, 2005,3(4): 227-36.
    [8] Li M, Li H, Li C, et al. Alpha-fetoprotein: a new member of intracellular signal molecules in regulation of the PI3K/AKT signaling in human hepatoma cell lines[J]. Int J Cancer, 2011, 12 8(3): 524-32.
    [9] Sambrook J, Frit sch EF, Manitis T. Molecular cloning: a laboratory mannul[M]. 2nd Editor. New York: Cold Spring Harbor Laboratory Press, 1989:1322-30.
    [10] Duda DG, Kozin SV, Kirkpatrick ND, et al. CXCL12 (SDF1α)- CXCR4/CXCR7 Pathway inhibition: An emerging sensitizer for anticancer therapies? [J]. Clin Cancer Res, 2011,17(8): 2074-80.
    [11] Xiang Z, Zeng Z, Tang Z, et al. Increased expression of vascular endothelial growth factor-C and nuclear CXCR4 in hepatocellular carcinoma is correlated with lymph node metastasis and poor outcome[J]. Cancer J, 2009,15(6): 519-25.
    [12] Chen G, Chen S, Wang X, et al. Inhibition of chemokine (CXC motif) ligand 12/chemokine (CXC motif) receptor 4 axis (CXCL12/CXCR4)-mediated cell migration by targeting mammalian target of rapamycin (mTOR) pathway in human gastric carcinoma cells[J]. J Biol Chem, 2012,287(15): 12132-41.
    [13] De Clercq E. The bicyclam AMD3100 story[J]. Nat Rev Drug Discov, 2003,2(7):581-7.
    [14] Li M, Li H, Li C, et al. Alpha fetoprotein is a novel proteinbinding partner for caspase-3 and blocks the apoptotic signaling pathway in human hepatoma cells[J]. Int J Cancer, 2009, 124(12): 28 45-54.
    [15] Li MS, Li PF, He SP, et al. The promoting molecular mechanism of alpha-fetoprotein on the growth of human hepatoma Bel7402 cell line[J]. World J Gastroenterol, 2002,8(3): 469-75.
    [16] Wang XW, Xie H. Alpha-fetoprotein enhances the proliferation of human hepatoma cells in vitro[J]. Life Sci, 1999,64(1): 17-23.
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出版历程
  • 收稿日期:  2012-11-28
  • 修回日期:  2013-03-19
  • 刊出日期:  2013-12-24

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