卡非佐米通过抑制骨髓瘤患者来源的间充质干细胞中的 notch1 活性，促进其成骨分化潜能。

Carfilzomib promotes the osteogenic differentiation potential of mesenchymal stem cells derived from myeloma patients by inhibiting notch1 activity in vitro.

机构信息

Department of Hematology, Second Affiliated Hospital of Soochow University, Suzhou, Jiang Su 215004, PR China.

Department of Cell Biology, Basic Medicine and Biology Science of Soochow University, Suzhou, Jiang Su 215004, PR China.

出版信息

Leuk Res. 2014 Aug;38(8):970-6. doi: 10.1016/j.leukres.2014.05.022. Epub 2014 Jun 4.

DOI:10.1016/j.leukres.2014.05.022

PMID:24939218

Abstract

Notch1 signaling plays a key role in the differentiation of mesenchymal stem cells (MSCs). Carfilzomib (CFZ), a second-generation proteasome inhibitor, has potent cytotoxicity against myeloma cells. In this study, we investigated the effects of CFZ on the osteogenic differentiation potential of MSCs derived from myeloma patients (MM-MSCs) in vitro. MM-MSCs showed decreased osteogenic differentiation ability, together with an impairment of notch1 deactivation. The notch1 inhibitor DAPT and the downregulation of notch1 by shRNA promoted osteogenesis in MM-MSCs. Additionally, CFZ treatment resulted in notch1 inhibition and enhanced osteogenesis in MM-MSCs. These findings suggest that CFZ stimulates osteogenesis via notch1 inhibition.

摘要

Notch1 信号通路在间充质干细胞（MSCs）的分化中起着关键作用。卡非佐米（CFZ），一种第二代蛋白酶体抑制剂，对骨髓瘤细胞具有很强的细胞毒性。在这项研究中，我们研究了 CFZ 对骨髓瘤患者来源的间充质干细胞（MM-MSCs）体外成骨分化潜能的影响。MM-MSCs 表现出成骨分化能力下降，同时 notch1 失活受损。Notch1 抑制剂 DAPT 和 shRNA 下调 notch1 促进 MM-MSCs 成骨。此外，CFZ 处理导致 notch1 抑制并增强 MM-MSCs 成骨。这些发现表明 CFZ 通过抑制 notch1 刺激成骨。