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As2O3联合AZT通过激活caspase-3通路抑制肝癌HepG2细胞的增殖
         
As2O3 in combination with AZT suppresses the proliferation of hepatoma HepG2 cells through activating caspase-3 pathway

摘    要
目的:探讨小剂量三氧化二砷(arsenic trioxide,As2O3)联合3'-叠氮-3'-脱氧胸腺嘧啶核苷(3'-azido-3'-deoxythymidine,AZT)对肝癌HepG2细胞增殖和凋亡的作用及其可能的作用机制。方法:应用MTT法检测不同浓度As2O3、AZT和As2O3联合AZT对人HepG2细胞的增殖抑制作用并计算联合指数,FCM法检测As2O3、AZT和As2O3联合AZT干预后HepG2细胞的凋亡率,RT-PCR法和蛋白质印迹法检测As2O3、AZT和As2O3联合AZT干预后HepG2细胞中caspase-3、Bcl-2和Bax mRNA及蛋白的表达水平。结果:As2O3联合AZT干预后,HepG2细胞的增殖抑制率高于各单药组(P < 0.05),As2O3联合AZT的联合指数<1,表现出明显的协同效应。As2O3联合AZT干预组HepG2细胞的凋亡率明显高于对照组(未进行药物干预)和各单药组(P < 0.05)。As2O3联合AZT干预组HepG2细胞中caspase-3和Bax mRNA及蛋白的表达水平明显高于对照组和各单药组(P < 0.05),As2O3联合AZT干预组HepG2细胞中Bcl-2 mRNA和蛋白的表达水平明显低于对照组(P < 0.05),As2O3联合AZT干预组HepG2细胞中Bax mRNA和蛋白表达水平与Bcl-2 mRNA和蛋白表达水平间的比值高于对照组(P < 0.05)。结论:As2O3联合AZT可协同抑制HepG2细胞的增殖,这一作用可能与诱导细胞凋亡、上调caspase-3和Bax表达以及下调Bcl-2表达有关。
标    签 肝肿瘤   细胞增殖   细胞凋亡   三氧化二砷   AZT   细胞,HepG2   Liver neoplasms   Cell proliferation   Apoptosis   Arsenic trioxide   AZT   Cell,HepG2  
 
Abstract
Objective: To investigate the effects of a small dose of arsenic trioxide (As2O3) combined with 3'-azido-3'-deoxythymidine (AZT) on proliferative inhibition and apoptosis of hepatoma HepG2 cells and their possible mechanism. Methods: The proliferation inhibition rates of HepG2 cells after treatment with different concentrations of As2O3 and AZT alone and their combination were detected by MTT assay. The combined index of As2O3 and AZT was calculated. The apoptotic rates of HepG2 cells after treatment with As2O3 and AZT alone and their combination were detected by flow cytometry (FCM), and the expression levels of caspase-3, Bcl-2 and Bax mRNAs and proteins were analyzed through RT-PCR and Western blotting, respectively. Results: The proliferation inhibition rate of HepG2 cells in combination of As2O3 and AZT group was higher than that in As2O3 and AZT alone groups (both P < 0.05). The value of combined index was less than 1, indicating obvious synergistic effect between As2O3 and AZT. The apoptotic rate of HepG2 cells after treatment with the combination of As2O3 and AZT was higher than those of the control cells (without any treatment) and As2O3 and AZT alone groups (all P < 0.05). The expression levels of caspase-3 and Bax mRNAs and proteins in combination of As2O3 and AZT group were higher than those of the control group (without any treatment) and As2O3 and AZT alone groups (all P < 0.05). The expression levels of Bcl-2 mRNA and protein in combination of As2O3 and AZT group were lower than those of As2O3 and AZT alone groups (both P < 0.05). The ratios of Bax/Bcl-2 mRNA and protein in combination of As2O3 and AZT group were higher than those of the control group (P < 0.05). Conclusion: As2O3 in combination with AZT has a synergistic effect on proliferative inhibition of HepG2 cells. This effect may be associated with induction of apoptosis, up-regulation of caspase-3 and Bax expressions, and down-regulation of Bcl-2 expression.

中图分类号 R735.7   DOI 10.3781/j.issn.1000-7431.2014.08.005

 
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所属栏目 基础研究

基金项目 2012年度甘肃省高等学校研究生导师科研项目(编号:1206-04)

收稿日期 2014/3/11

修改稿日期 2014/5/19

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引用该论文: LIU Yu,YUAN Ling-yan,CHU Hui-yuan,CHEN Che. As2O3 in combination with AZT suppresses the proliferation of hepatoma HepG2 cells through activating caspase-3 pathway[J]. Tumor, 2014, 34(8): 705~711
刘玉,原凌燕,楚慧媛,陈彻. As2O3联合AZT通过激活caspase-3通路抑制肝癌HepG2细胞的增殖[J]. 肿瘤, 2014, 34(8): 705~711


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参考文献
【1】张思维,郑荣寿,李霓,等.中国肝癌发病的趋势分析和预测[J].中华预防医学杂志, 2012, 46(7):587-589.
 
【2】Abou-Alfa GK, Huitzil-Melendez FD, O'Reilly EM, et al. Current management of advanced hepatocellular carcinoma[J]. Gastrointest Cancer Res, 2008, 2(2):64-70.
 
【3】Thomas M. Molecular targeted therapy for hepatocellular carcinoma[J]. J Gastroenterol, 2009, 44(19):136-141.
 
【4】Ma Y, Wang J, Liu L, et al. Genistein potentiates the effect of arsenic trioxide against human hepatocellular carcinoma:role of Akt and nuclear factor-κB[J]. Cancer Lett, 2011, 301(1):75-84.
 
【5】杨鸿武,杨贤东,关宏伟.三氧化二砷逆转人胃癌细胞SGC7901/ADR耐药性的作用机制[J].肿瘤, 2006, 26(11):994-996.
 
【6】Wang X, Gao P, Long M, et al. Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide[J]. Med Oncol, 2011, 28(4):1225-1254.
 
【7】高敏,周福祥,谢丛华,等.端粒酶抑制剂叠氮胸苷对HeLa细胞放射性DNA损伤修复的影响[J].癌变·畸变·突变, 2007, 19(6):448-452.
 
【8】周遵艳,骆志国,戴静,等.叠氮胸苷对人胶质瘤细胞辐射后DNA双链损伤修复的影响[J].实用癌症杂志, 2005, 20(5):449-451.
 
【9】Chen C, Zhang Y, Wang Y, et al. Synergic effect of 3'-azido-3'-deoxythymidine and arsenic trioxide in suppressing hepatoma cells[J]. Anticancer Drugs, 2011, 22(5):435-443.
 
【10】王长安.三氧化二砷抗肿瘤机制研究进展[J].肿瘤基础与临床, 2011, 24(5):458-460.
 
【11】张旭霞,孙延庆,魏小芳,等.大黄素对人慢性髓细胞性白血病K562细胞增殖与凋亡及c-myc基因表达的影响[J].中华肿瘤防治杂志, 2009, 16(20):1541-1545.
 
【12】Lizzi AR, D'Alessandro AM, Zeolla N, et al. The effect of AZT and chloroquine on the activities of ricin and a saporin-transferrin chimeric toxin[J], Biochem Pharmacol, 2005, 70(4):560-569.
 
【13】Jia Y, Liu D, Xiao D, et al. Expression of AFP and STAT3 is involved in arsenic trioxide-induced apoptosis and inhibition of proliferation in AFPproducing gastric cancer cells[J]. PLoS One, 2013, 8(1):e54774.
 
【14】Wang W, Adachi M, Zhang R, et al. A novel combination therapy with arsenic trioxide and parthenolide against pancreatic cancer cells[J]. Pancreas, 2009, 38(4):114-123.
 
【15】刘志宇,田蓝天,王巍.三氧化二砷联合小白菊内酯的抗胰腺癌作用[J].哈尔滨医科大学学报, 2011, 45(5):412-415.
 
【16】Liu L, Chen R, Huang S, et al. miR-153 sensitized the K562 cells to As2O3-induced apoptosis[J]. Med Oncol, 2012, 29(1):243-247.
 
【17】靳蕊蕊,晁荣,席亚明,等. AZT对白血病细胞株KG-1a细胞增殖和端粒酶活性的影响[J],中国实验血液学杂志, 2012, 20(2):277-281.
 
【18】伍婧,罗荣城,张华,等.索拉菲尼联合三氧化二砷对肝癌细胞株的抑制作用[J].南方医科大学学报, 2008, 28(4):639-645.
 
【19】周艳,于嘉伟,邬红霞,等.三氧化二砷联合羟基喜树碱对肝癌细胞SMMC-7721的作用[J].山东医药, 2009, 49(51):49-51.
 
【20】张翠娟,周庚寅,喻芳,等. 5-脱氧杂氮胞苷对HepG2肝癌细胞恶性表型及caspase-3和bcl-2表达的影响[J].临床与实验病理学杂志, 2005, 21(1):103-106.
 
【21】Iizaka T, Tsuji M, Oyamada H, et al. Interaction between caspase-8 activation and endoplasmic reticulum stress in glycochenodeoxycholic acidinduced apoptotic HepG 2 cells[J]. Toxicology, 2007, 241(3):146-156.
 
【22】Zhao H, Yenari MA, Cheng D, et al. Bcl-2 overexpression protects against neuron loss within the ischemic margin following experimental stroke and inhibits cytochrome c translocation and caspase-3 activity[J]. J Neurochem, 2003, 85(4):1026-1036.
 
【23】Lin HH, Chen JH, Huang CC, et al. Apoptotic effect of 3, 4-dihydroxybenzoic acid on human gastric carcinoma cells involving JNK/p38 MAPK signaling activation[J]. Int J Cancer, 2007, 120(11):2306-2316.
 
【24】Scorrano L, Korsmeyer SJ. Mechanisms of cytochrome c release by proapoptotic Bcl-2 family members[J]. Biochem Biophys Res Commun, 2003, 304(3):437-444.
 
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