中文摘要：

目的：分析蛋白酶体抑制剂PS-341对多发性骨髓瘤（MM）骨髓间充质干细胞（MSCs）凋亡及其对IL-6、IL-1β、SCF细胞因子表达的影响。方法：含10％FBS的1640培养液培养得到MSCs，流式细胞术（FCM）鉴定所培养细胞的表型，以终浓度分别为0nmol／L、50nmol／L、100nmol／L、150nmol／L、200nmol／L的PS-341作用MSCs 4h，光学显微镜观察细胞形态改变，荧光显微镜下Annexin V—FITC／PI双染法观察细胞凋亡，反转录聚合酶链反应（RT—PCR）检测IL-6、IL-1β、SCF细胞因子表达的变化。结果：PS-341可诱导MSCs凋亡，与其浓度成正比；与对照组（Onmol／LPS-341）比较，浓度分别为50nmol／L、100nmol／L、150nmol／L、200nmol／L的PS-341作用MSCs 4h后明显抑制IL-6、IL-1β、SCF的表达（P〈0．05）；PS～341对IL-6和SCF的抑制与PS-341浓度成正相关（P〈0．05），在初发／难治复发和完全缓解（CR）两组患者间均无显著差异；对IL～1β的抑制在CR组较初发／难治复发组更明显（P〈0．05）；PS-341作用后IL—1β表达的强弱对IL-6及SCF的表达无影响。结论：PS-341诱导MM患者MSCs凋亡和抑制其IL-6、IL-1β、SCF的表达，是PS-341有效治疗MM的靶点之一。

英文摘要：

Objective.To analyse the apoptosis and expressions of cytokines IL-6,IL-1β and SCF of mesenchymal stem cells（MSCs）,which was derived from Multiple Myeloma （MM） treated with proteasome inhibitor PS-341. Meth ods ：MSCs were incubated in the culture of RPMI1640 with 10% fetal bovine serum（FBS） and were determined by flow cytometric （FCM）,then MSCs were exposed to 0 nmol/L ,50 nmol/L, 100 nmol/L, 150 nmol/L ,200 nmol/L PS-341 for 4 hours,then cells apoptosis were analyzed by inverted light microscopy and fluorescence microscope with annexin VFITC/PI dual staining,and reverse transcription polymerse chain reaction （RT-PCR） was performed to detect the expressions of IL-6,IL-1β and SCF. Results： PS-341 induced MSCs apoptosis in a dose-dependent manner. After PS-341 treated expressions of IL-6,IL-1β,SCF of MSCs were decreased（P〈0.05）,There were no statistics differences of IL-6 and SCF expression between refractory/relapsed group and complete remission（CR）group and PS-341 downregulated the expressions of IL-6 and SCF of MSCs in a dose-dependent manner;IL-1β was significantly inhibited in CR group compared with that in refractory/relapsed group; there were no significant relationship between the expressions of IL-6 and SCF and the expression of IL-1β. Conclusions ：Proteasome inhibitor PS-341 can induce MSCs apoptosis and inhibited the expressions of IL-6,IL-1β and SCF,which might be one of mechanisms and targets for MM treatment.