期刊
EUROPEAN JOURNAL OF HAEMATOLOGY
卷 85, 期 2, 页码 99-107出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1600-0609.2010.01450.x
关键词
proteasome; multiple myeloma; apoptosis; NF-kappa B; cell cycle
类别
Objectives: The ubiquitin-proteasome system emerged as a new therapeutic target in cancer treatment. The purpose of this study was to elucidate the effects of the novel proteasome inhibitor BSc2118 on t(4;14) positive and negative multiple myeloma (MM) cells and normal peripheral blood mononuclear cells (PBMNC). Methods: Human MM cell lines OPM-2, RPMI-8226, and U266 and primary MM cells from bone marrow aspirates were exposed to BSc2118. Cytotoxicity levels were evaluated using the MTT-test. BSc2118-induced apoptosis was analyzed by annexin-V assay. Further methods used included proteasomal activity determination, cell cycle analysis, western blot, and transcription factor assays. Results: In OPM-2, RPMI-8226, U266 cell lines and primary MM cells, BSc2118 caused dose-dependent growth inhibitory effects. After 48 h, dose-dependent apoptosis occurred both in cell lines and primary myeloma cells irrespective of t(4;14). A significant G2-M cell cycle arrest occurred after 24 h. Furthermore, we observed a marked inhibition of intracellular proteasome activity, an increase in intracellular p21 levels, and an inhibition of NF-kappa B activation. The toxicity against PBMNC remained low, suggesting a broad therapeutic range of this agent. Conclusion: Taken together, BSc2118 shows significant antimyeloma activity and may be considered as a promising agent in cancer drug development.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据