Department of Physiology, University of Zagreb, Zagreb, Croatia.
Leuk Lymphoma. 2012 Nov;53(11):2253-61. doi: 10.3109/10428194.2012.684351. Epub 2012 May 21.
Rapamycin and its derivatives have been proposed in the treatment of leukemia based on their cytostatic effects, but their possible role in differentiation therapy is less explored. The aim of the present study was to investigate the possible beneficial effects of the combination of rapamycin and dimethyl sulfoxide (DMSO) on growth arrest and differentiation of acute myelogenous leukemia (AML) cells. In myeloblastic HL-60, promyelocytic NB4, monocytic U937, immature KG-1 and erythro-megakaryocytic K562 cell lines, rapamycin alone had modest inhibitory effects, DMSO inhibited proliferation in a dose-dependent manner, and the combination of rapamycin and DMSO reduced the number of viable cells significantly more than either agent alone. In NB4 cells, rapamycin had no statistically significant effects on the DMSO-mediated increase in expression of CD11b, but increased apoptosis. These results demonstrate that rapamycin enhances DMSO-mediated growth arrest, and suggest that mTOR (mammalian target of rapamycin) inhibitors may have beneficial effects in differentiation therapy of AML.
雷帕霉素及其衍生物基于其细胞抑制作用被提出用于治疗白血病，但它们在分化治疗中的可能作用尚未得到充分探索。本研究旨在探讨雷帕霉素和二甲基亚砜 (DMSO) 联合应用对急性髓系白血病 (AML) 细胞生长抑制和分化的可能有益作用。在髓样 HL-60、早幼粒细胞 NB4、单核 U937、幼稚 KG-1 和红巨核细胞 K562 细胞系中，雷帕霉素单独具有适度的抑制作用，DMSO 呈剂量依赖性抑制增殖，雷帕霉素和 DMSO 的联合应用比单独使用任一药物更显著地减少活细胞数。在 NB4 细胞中，雷帕霉素对 DMSO 介导的 CD11b 表达增加没有统计学上的显著影响，但增加了细胞凋亡。这些结果表明雷帕霉素增强了 DMSO 介导的生长抑制，并提示 mTOR（雷帕霉素的哺乳动物靶标）抑制剂在 AML 的分化治疗中可能具有有益作用。
