TRAIL联合喜树碱体外诱导肝癌细胞凋亡的研究
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吕国悦

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Study of TRAIL combined with camptothecin in induction of apoptosis in hepatocellular carcinoma cell lines
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    摘要:

    摘要:目的:探讨喜树碱增加TRAIL诱导肝癌细胞HepG2和Hep3B凋亡能力的分子机制。
    方法:应用流式细胞仪分析TRAIL单独或联合应用喜树碱对肝癌细胞系HepG2和Hep3B细胞凋亡的影响;Western blot检测HepG2和Hep3B细胞在处理前后凋亡信号传导蛋白caspase-8,caspase-3,caspase-9,DR4,DR5,DcR1,c-FLIP,RIP,cytc,Smac和Bid表达的变化。
    结果:喜树碱能增强TRAIL诱导肝癌细胞凋亡的能力,两者联用具有明显的协同作用。喜树碱预先处理能下调c-FLIP及RIP的表达及增加cytc,Smac,Bid的表达,但对DR4,DR5,DcR1的表达无明显影响。
    结论:TRAIL联合喜树碱可以诱导肝癌细胞凋亡;其机制是下调c-FLIP及RIP的表达,活化凋亡发生的死亡受体通路,上调Bid的表达激活线粒体通路。死亡受体的表达不参与这一变化过程。

    Abstract:

    Abstract:Objective:To investigate the molecular mechanism of camptothecin enhancement of TRAIL-induced apoptosis in hepatocellular carcinoma cell lines.
    Methods :The HepG2 and Hep3B cell cycles were analysed by flow cytometry after co-treated with camptothecin and TRAIL, and the expression of signal transduction protein, such as Caspase-8, Caspase-3, Caspase-9, DR4, DR5, DcR1, c-FLIP, RIP, Cytc, Smac, Bid were detected by Western blot before and after the treatment.
    Results:Pretreatment with lower dose of Camptothecin could increase the sensitivity of HepG2 and Hep3B cells to TRAIL-induced apoptosis, and could downregulate the expression of c-FLIP and RIP, upregulate the expression of Cytc, Smac and Bid, but had no effect on the expression of DR4, DR5 and DcR1.
    Conclusions:Camptothecin could sensitize HepG2 and Hep3B cells to TRAIL-induced apoptosis, and the mechanism is by downregulation of c-FLIP and RIP, activation of apoptosis death receptor pathway, upregulation of Bid and amplification of the mitochondrial pathway. The expression of death receptor not involved in this process.

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王广义, 吕国悦, 张平, 张强, 纪柏, 孟宪瑛. TRAIL联合喜树碱体外诱导肝癌细胞凋亡的研究[J].中国普通外科杂志,2008,17(1):21-24.
DOI:10.7659/j. issn.1005-6947.2008.01.017

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  • 在线发布日期: 2008-01-25