蛋白酶体抑制剂PS-341对多发性骨髓瘤骨髓间充质干细胞多种细胞因子表达的影响_医学论文.docVIP

蛋白酶体抑制剂PS-341对多发性骨髓瘤骨髓间充质干细胞多种细胞因子表达的影响_医学论文 蛋白酶体抑制剂PS-341对多发性骨髓瘤骨髓间充质干细胞多种细胞因子表达的影响_医学论文 作者：林如峰，陆化，刘澎，沈文怡，张建富，吴雨洁，费小明，李建勇【摘要】 为了探讨蛋白酶体抑制剂PS-341(bortezomib，velcade)对多发性骨髓瘤（MM）患者间充质干细胞（MSC）细胞因子分泌的影响，用含10% FBS的RPMI 1640培养液培养11例MM患者MSC，细胞数达5-10×105时以终浓度50 nmol/L的PS-341作用4小时，用逆转录聚合酶链反应（RT-PCR）检测IL-6、IL-1β、SCF细胞因子表达。结果表明： PS-341作用后MM病人MSC细胞因子的表达有显著下降，IL-6、IL-1β、SCF的表达与对照组比较，其显著性检验结果分别为0.05、0.01、0.05，其中 IL-1β尤为明显；难治复发组与缓解组比较，IL-1β的表达有显著差异，完全缓解（CR）组IL-1β表达受抑制更明显，IL-6、SCF两组间表达无明显差异；PS-341治疗的1例患者MSC在PS-341作用后IL-1β未见表达；IL-1β的表达与否对IL-6、SCF的表达无影响。结论： 蛋白酶体抑制剂PS-341下调MM患者MSC IL-6、IL-1β、SCF细胞因子的表达。 【关键词】 多发性骨髓瘤 　　Effects of Proteasome Inhibitor PS-341 on the Multiple Cytokine Expressions of Mesenchymal Stem Cells from Bone Marrow in Patients with Multiple Myeloma 　　Abstract To explore the effects of proteasome inhibitor PS-341 on the cytokine expressions of mesenchymal stem cells (MSC) in patients with multiple myeloma（MM），MSCs of 11 patients were cultured in medium of RPMI 1640 containing 10% FBS. When cells grew to 5×105-1×106，cells were exposed to 50 nmol/L PS-341 for 4 hours，then harvested. The expressions of IL-6，IL-1β and SCF were detected by RT-PCR. The results indicated that after treatment with PS-341 the expressions of IL-6，IL-1β and SCF of MSCs decreased markedly，especially that of IL-1β，compared with control (0.05、0.01、0.05，respectively). There were obviously differences of IL-1β expression between refractory/relapsed group and complete remission（CR）group and IL-1β expression was inhibited more seriously in CR group，whereas there were no significant differences of IL-6 and SCF expression between two groups；IL-1β expression of patients treated with PS-341 was not detected；there were not effects of IL-1β expression on expressions of IL-6 and SCF. It is concluded that proteasome inhibitor PS-341 downregulated the expressions of IL-6，IL-1β and SCF of MSCs in patients with MM . 　　Key words proteasome inhibitor PS-341；multiple myeloma；mesenchymal stem cell；interlukin-6；inte