Flavopiridol诱导多发性骨髓瘤细胞凋亡的分子机制  

Molecular mechanisms of flavopiridol in inducing apoptosis in multiple myeloma

作　　者：王孟昌[1] 张斌 

机构地区：[1]西安交通大学医学院第一附属医院血液科,陕西西安710061 [2]美国Maryland癌症中心

出　　处：《西安交通大学学报（医学版）》2011年第2期201-204,共4页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：国家自然科学基金资助项目(No.81071952)~~

摘　　要：目的探讨flavopiridol诱导多发性骨髓瘤(MM)细胞凋亡的分子机制。方法以TUNEL法检测细胞凋亡,Western blot测定Mcl-1、CyclinD2、Bcl-XL、Bag-1和XIAP等。结果在临床剂量的flavopiridol浓度下,MM细胞系在加药后3 h内出现快速凋亡。不同剂量的flavopiridol均可快速诱导Mcl-1表达下调和CTD磷酸化的抑制,flavopiridol抑制CTD磷酸化的剂量与其抑制Mcl-1表达的剂量密切相关。该剂量也是其诱导MM细胞凋亡的剂量。转录抑制因子放线菌素D及flavopiridol均能抑制Mcl-1表达,并可诱导原代MM细胞凋亡。结论转录抑制因子放线菌素D和CDK抑制剂flavopiridol诱导MM细胞凋亡可能与其抑制CTD磷酸化,从而抑制Mcl-1的mRNA以及蛋白质水平有关。Objective To study the molecular mechanisms of flavopiridol in inducing apoptosis in multiple myeloma（MM）.Methods TUNEL methods were used to detect cell apoptosis;Western blot was used to determine the expression levels of myeloid cell leukemia-1（Mcl-1）,CyclinD2,Bcl-XL,Bag-1 and XIAP.Results The clinical concentration of flavopiridol resulted in rapid apoptosis after dosing within 3h in MM cell lines.Different doses of flavopiridol could induce rapid down-expression of Mcl-1 and inhibition of CTD phosphorylation.The dose of flavopiridol＇s inhibition on CTD phosphorylation was closely related to the dose of its inhibition on Mcl-1 expression.This dose was also the one that induced apoptosis in MM cells.Transcription inhibitor actinomycin D and flavopiridol could also inhibit the expression of Mcl-1 and induce apoptosis in primary MM.Conclusion Apoptosis of myeloma cells induced by transcription inhibitor actinomycin D and CDK inhibitor flavopiridol may be related to their inhibition on CTD phosphorylation,thereby inhibiting Mcl-1 at the mRNA and protein levels.

关 键 词：多发性骨髓瘤 FLAVOPIRIDOL MCL-1 BCL-XL BAG-1 CYCLIND2 

分 类 号：R733.3[医药卫生—肿瘤]