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

作　　者：朱秀丽[1] 江莲[1] 陈健[1] 刘翠萍[1] 刁玉巧[1] 李梅[1] 郑钰[1] 

机构地区：[1]河北医科大学第四医院儿科,石家庄市050011

出　　处：《中国肿瘤临床》2012年第22期1757-1760,共4页Chinese Journal of Clinical Oncology

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、Bel-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。Objecti ve：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.

关 键 词：x-连锁凋亡抑制蛋白Embelin T淋巴瘤细胞增殖抑制 MTS法 

分 类 号：R733.1[医药卫生—肿瘤]