Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, United States.
Leuk Res. 2010 Mar;34(3):344-51. doi: 10.1016/j.leukres.2009.06.035. Epub 2009 Jul 30.
Thalidomide has emerged as an effective agent for treating multiple myeloma, however the precise mechanism of action remains unknown. Agents known to target the isoprenoid biosynthetic pathway (IBP) can have cytotoxic effects in myeloma cells. The interactions between thalidomide and IBP inhibitors in human multiple myeloma cells were evaluated. Enhanced cytotoxicity and induction of apoptosis were observed in RPMI-8226 cells. Examination of intracellular levels of farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP) revealed a wide variance in basal levels and response to IBP inhibitors. These findings provide a mechanism for the differential sensitivity of myeloma cells to pharmacologic manipulation of the IBP.
沙利度胺已成为治疗多发性骨髓瘤的有效药物，但其确切作用机制尚不清楚。已知靶向异戊烯基生物合成途径（IBP）的药物可对骨髓瘤细胞产生细胞毒性作用。评估了沙利度胺和人多发性骨髓瘤细胞中 IBP 抑制剂的相互作用。在 RPMI-8226 细胞中观察到增强的细胞毒性和细胞凋亡诱导。细胞内法呢基焦磷酸（FPP）和香叶基焦磷酸（GGPP）水平的检测显示出基础水平和对 IBP 抑制剂反应的广泛差异。这些发现为骨髓瘤细胞对 IBP 药理作用的敏感性差异提供了机制。
