TRAIL对人多发性骨髓瘤细胞株RPMI8226黏附和凋亡的影响及其作用机制的初步探讨  

Preliminary Study on the Effect of TRAIL on Adhesion and Apoptosis of Multiple Myeloma Cell Line RPMI8226 and Its Mechanism

作　　者：王福旭[1] 赵芳[2] 潘崚[1] 张学军[1] 罗建民[1] 杨敬慈[1] 姚丽[1] 杜行严[1] 董作仁[1] 

机构地区：[1]河北医科大学第二医院血液科,河北石家庄050000 [2]沧州市中心医院血液科,河北沧州061001

出　　处：《中国实验血液学杂志》2010年第1期96-102,共7页Journal of Experimental Hematology

摘　　要：本研究探讨肿瘤坏死因子相关凋亡诱导配体TRAIL对人多发性骨髓瘤细胞系RMPI8226的生长抑制作用,对细胞黏附和凋亡的影响及其作用机制。用MTT法检测TRALL对RPMI8226黏附功能和生长的影响;用AnnexinⅤ/PI检测细胞凋亡;流式细胞学检测细胞表面黏附分子的表达;RT-PCR法测定凋亡相关基因表达水平和Western blot法检测凋亡相关蛋白表达。结果表明:TRAIL抑制RPMI8226细胞生长;可诱导RPMI8226细胞凋亡,并伴有抗凋亡基因Mcl-1、XIAP、cFLIP、CARP1、CARP2和Bcl-2mRNA表达水平下降,促凋亡基因Bax mRNA表达水平升高;RPMI8226细胞内的凋亡执行蛋白caspase-3和NF-κB P65(RelA)表达水平随TRAIL浓度的增加而下降。此外,TRAIL明显上调了RPMI8226细胞表面黏附分子CXCR4的表达。结论TRAIL上调人多发性骨髓瘤细胞株RPMI8226细胞表面的黏附分子CXCR4表达水平。TRAIL可诱导人多发性骨髓瘤细胞株RPMI8226凋亡。在一定的浓度范围内,TRAIL对人骨髓瘤细胞株RPMI8226的生长抑制呈时间-剂量依赖性。The present study was purposed to investigate the inhibition effect of tumor necrosis factor-related apoptosis inducing ligand （TRAIL） on growth of RPMI8226 cells and adhesion between RPMI8226 cells and bone marrow stroma cells （BMSC）, and to explore its mechanism as well. The inhibition effects of TRAIL on cells growth and adhesion were assayed by MTT; cell apoptosis was detected by Annexin V and PI; expression of genes bax, bcl-2, mcl-1, CARPI, CARP2, XIAP and cFLIP were determined by semi-quantitative RT-PCR; apoptosis-related protein expression was detected by Western blot. The results showed that TRAIL inhibited the proliferation of RPMI8226 cells in dose- and time-dependent manners. TRAIL induced apoptosis in RPMI8226 cells, the expression level of genes bcl-2, mcl-1, CARP1, CARP2, XIAP and cFLIP decreased, while the expression level of Bax increased, but the expression level of caspase-3 and NF-KB P65 （RelA）proteins decreased. Moreover, TRAIL up-regulated the expression level of adherent molecule CXCR4 in RPMI8226 cells significantly. It is concluded that TRA1L up-regulated the expression level of adherent molecule CXCR4 in RPMI8226 cells significantly, and induced the apoptosis of RPMI8226 cells. Growth inhibition effect of TRAIL on RPMI8226 cells is in dose- and time-dependent manners.

关 键 词：肿瘤坏死因子相关凋亡诱导配体 多发性骨髓瘤 RPMl8226 细胞凋亡 黏附 骨髓基质细胞 

分 类 号：R733.3[医药卫生—肿瘤]