β-catenin特异性抑制剂XAV939对套细胞淋巴瘤Jeko-1细胞增殖抑制的实验研究  

Antiproliferative Effect of Specific Inhibitor XAV939 for β-catenin on MCL Jeko-1 Cells

作　　者：何金水[1] 黄轶群[2] 翁剑鸣[3] 肖丽云[1] 翁开枝[1] 马旭东[2] 

机构地区：[1]福建医科大学附属漳州市医院儿科,福建漳州363000 [2]福建医科大学附属漳州市医院血液科,福建漳州363000 [3]福建医科大学附属漳州市医院病理科,福建漳州363000

出　　处：《中国实验血液学杂志》2015年第2期411-415,共5页Journal of Experimental Hematology

基　　金：福建省卫生厅青年科研课题(2012-2-114)

摘　　要：目的:通过短发夹RNA(shRNA)干扰β-catenin基因的表达及使用β-catenin特异性抑制剂XAV939作用于套细胞淋巴瘤(MCL)Jeko-1细胞株,了解特异性抑制β-catenin活性对Jeko-1细胞增殖及细胞凋亡的影响。方法:将构建β-catenin shRNA真核表达载体转染Jeko-1细胞,应用RT-PCR和Western blot的方法鉴定干扰效果,用不同浓度XAV939处理MCL细胞株Jeko-1;应用MTT法绘制细胞生长曲线,流式细胞术分析细胞凋亡,Western blot检测凋亡相关蛋白BCL-2、BAX、Cyclin D1、C-MYC、caspase-3表达水平的变化。结果:shRNA转染48 h后,RTPCR、Western blot检测发现,Jeko-1细胞的β-catenin的mRNA、蛋白表达下降;无论使用shRNA或抑制剂处理,均可抑制Jeko-1细胞增殖,促进其凋亡;Western blot检测显示,凋亡相关蛋白BCL-2、Cyclin D1、C-MYC的表达下降,而BAX、caspase-3表达上升。结论:特异性抑制β-catenin活性能有效地抑制Jeko-1细胞的增殖,并诱导细胞凋亡。Objective：To investigate the effect of short hairpin RNA （shRNA） and XAV939, a specific inhibitor for β-catenin, on growth and apoptosis of mantle cell lymphoma（MCL） Jeko-1 cell line. Methods：β-catenin shRNA eukaryotic expression vector was transfected into Jeko-1 cells, the antiproliferative effect of shRNA on Jeko-1 cells was detected by RT-PCR and Western blot. The proliferation inhibitory rate of Jeko-1 cells treated by different doses of XAV939 was assayed by MTT method; the level of apoptosis of Jeko-1 cells was detected by flow cytometry; the expression levels of apoptosis-related protein BCL-2, BAX, CyclinD1, C-MYC and Caspase-3 in Jeko-1 cells were determined by Western blot. Results： The expression offl-catenin mRNA and growth of Jeko-1 cell line were inhibited by shRNA; after Jeko-1 cells treated with 0,2 and 8/μmol/L XAV939 for 48 hours, the cell proliferation rate decreased, while the cell apoptosis rate increased, the expressions of apoptosis-related protein BCL-2,CyclinDI and C-MYC were down-regulated, on the contrary, the expression of BAX and caspase-3 were up-regulated. Conclusion： The specific inhibition of β-catenin can inhibit Jeko-1 cell proliferation and promote the cell apoptosis.

关 键 词：短发夹核糖核酸 XAV939抑制剂 β-连环素套细胞淋巴瘤 细胞凋亡 

分 类 号：R733.1[医药卫生—肿瘤]