朱秀丽, 江莲, 陈健, 刘翠萍, 刁玉巧, 李梅, 郑钰. XIAP抑制剂Embelin对人T淋巴瘤细胞Jurkat增殖抑制作用[J]. 中国肿瘤临床, 2012, 39(22): 1757-1760. DOI: 10.3969/j.issn.1000-8179.2012.22.017
引用本文: 朱秀丽, 江莲, 陈健, 刘翠萍, 刁玉巧, 李梅, 郑钰. XIAP抑制剂Embelin对人T淋巴瘤细胞Jurkat增殖抑制作用[J]. 中国肿瘤临床, 2012, 39(22): 1757-1760. DOI: 10.3969/j.issn.1000-8179.2012.22.017
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Xiuli ZHU, Lian JIANG, Jian CHEN, Cuiping LIU, Yuqiao DIAO, Mei LI, Yu ZHENG. Embelin Inhibition of Human Acute T-Cell Lymphoblastic Leukemia in Jurkat Cells[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2012, 39(22): 1757-1760. DOI: 10.3969/j.issn.1000-8179.2012.22.017
Citation: Xiuli ZHU, Lian JIANG, Jian CHEN, Cuiping LIU, Yuqiao DIAO, Mei LI, Yu ZHENG. Embelin Inhibition of Human Acute T-Cell Lymphoblastic Leukemia in Jurkat Cells[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2012, 39(22): 1757-1760. DOI: 10.3969/j.issn.1000-8179.2012.22.017
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XIAP抑制剂Embelin对人T淋巴瘤细胞Jurkat增殖抑制作用

Embelin Inhibition of Human Acute T-Cell Lymphoblastic Leukemia in Jurkat Cells

    摘要
  • 摘要:
      目的   研究XIAP抑制剂Embelin体外对人T淋巴瘤细胞Jurkat增殖的影响，并探讨其作用机制。
      方法  应用MTS法分析不同浓度Embelin对人T淋巴瘤细胞增殖的影响；光学显微镜下观察经Embelin处理后细胞形态学的改变；经Annexin V/PI双染后用流式细胞术检测Embelin对Jurkat细胞凋亡的影响；Western blot方法检测Embelin作用后细胞XIAP、PARP、Caspase-3、Caspase-8、Caspase-9、促凋亡蛋白Bax和抗凋亡蛋白Bcl-xl、Bcl-2表达的变化。
      结果  Emebeli对人白血病细胞具有显著增殖抑制作用（P < 0.05）；Caspase-3抑制剂z-DEVD-fmk，Caspase-9抑制剂Ac-LEHD-CHO能显著下调这种增殖抑制作用。经不同浓度Emebelin处理24 h后，Jurkat细胞凋亡率明显增高，与未处理组比较有显著性差异（P < 0.01）；经Emebelin处理24 h后，Jurkat细胞出现PARP、Caspase3、9裂解片段，且Bax蛋白表达上调，Bcl-2和Bcl-xL蛋白表达水平下调。
      结论  Embelin在体外可明显抑制人T淋巴瘤细胞Jurkat的增殖，诱导细胞凋亡，其机制可能是通过拮抗XIAP的作用，激活Caspase依赖性的细胞凋亡内源途径而诱导Jurkat细胞发生凋亡。

     

    Abstract:
      Objective   This work aimed to determine the effect of the XIAP inhibitor embelin on the proliferation of human acute T-cell lymphoblastic leukemia in Jurkat cells and to elucidate the mechanisms involved.
      Methods  The growth suppression of Jurkat cells by embelin was analyzed using the MTS 3(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt assay. The morphological changes of the cancer cells were observed by light microscopy. The apoptotic rate was evaluated by flow cytometry after annexin/propidium iodide double staining. Western blot analysis was performed to assess the expression of the X-linked inhibitor of apoptosis (XIAP), poly adenosine diphosphate diphosphate phosphoribosyl transferase (PARP), caspase-3, caspase-8, caspase-9, and the pro-apoptotic factor Bax as well as the pro-survival factors Bcl-xL and Bcl-2.
      Results  Embelin significantly inhibited the proliferation of the human leukemia cells (P < 0.05). However, the caspase-3 and caspase-9 inhibitors, z-DEVD-fmk and Ac-LEHD-CHO, respectively, could reverse the action of embelin. The apoptosis of Jurkat cells was significantly increased after 24 h of embelin treatment as compared with that of the control group (P < 0.05). Furthermore, the cleavage of PARP, caspase-3, and caspase-9 was observed (P < 0.05). Moreover, Bax expression was upregulated while Bcl-2 and Bcl-xL levels were decreased.
      Conclusion   Embelin can significantly inhibit the proliferation of human T-cell lymphoma in the Jurkat cell line by antagonizing the endogenous XIAP pathway that activates caspase-dependent apoptosis in Jurkat cells.

     

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