| 王孟昌1，张 斌2 Flavopiridol诱导多发性骨髓瘤细胞凋亡的分子机制 |
| 论文编辑部-新丝路理论网 2011-03-31 15:41:14 作者:中华医学之家：http://www.xinxi85.com 来源: 文字大小:[大][中][小] |
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Title:
Molecular mechanisms of flavopiridol in inducing apoptosis in multiple myeloma
- 文章编号:
- 1671-8259(2011)02-0201-04
- 作者:
- 王孟昌1; 张 斌2
- 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，Baltimore 21205, USA
- Author(s):
- WANG Meng-chang1; ZHANG Bin2
- 1. Department of Hematology, the First Affiliated Hospital, Medical School of Xi’an Jiaotong University, Xi’an 710061, China; 2. University of Maryland Cancer Center, Baltimore 21205, USA
- 关键词:
- ; 多发性骨髓瘤; flavopiridol; Mcl-1; Bcl-XL; Bag-1; CyclinD2
- Keywords:
- ; multiple myeloma; flavopiridol; Mcl-1; Bcl-XL; Bag-1; CyclinD2
- 分类号:
- R733.3
- DOI:
- -
- 文献标识码:
- A
- 摘要:
- 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3h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。
- Abstract:
- ABSTRACT: 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.
参考文献/References
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基金项目：国家自然科学基金资助项目(No.81071952)
Supported by the National Natural Science Foundation of China (No.81071952)
作者简介：王孟昌(1965-)，男(汉族)，博士，副教授. 研究方向：多发性骨髓瘤的发病机制. E-mail: swallow3956@yahoo.com.cn
中华医学之家：http://www.xinxi85.com
投稿信箱：zhyxzj85@163.com
联系电话：029--85327298 主编QQ：693891972 |
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