Gu Chunhong, Ye Teng, Wells Richard A
Discipline of Molecular and Cellular Biology, Sunnybrook Research Institute, Toronto, Ont., Canada M4N 3M5.
Leuk Res. 2006 Nov;30(11):1447-51. doi: 10.1016/j.leukres.2006.03.029. Epub 2006 May 15.
We have previously shown that troglitazone (TG) induces apoptosis in acute myelogenous leukaemia (AML) cell lines. Here we show that normal bone marrow and mobilized peripheral blood progenitors are highly resistant to TG at concentrations up to 100 microM, while primary cultures of AML bone marrow show significant decline in viability at >7.5 microM TG. The combination of standard cytotoxic agents (daunorubicin, etoposide, and cytarabine) with TG is synergistic in six AML cell lines, with the strongest synergy being exhibited when cells are pretreated with TG for 24h prior to addition of the cytotoxic agent. Significant declines in IC(50) for the cytotoxic agents are seen at nanomolar concentrations of TG. The in vitro synergy between TG and the cytotoxic drugs used in AML therapy provides a basis for in vivo evaluation of these combinations.
我们之前已表明，曲格列酮（TG）可诱导急性髓性白血病（AML）细胞系发生凋亡。在此我们表明，正常骨髓和动员的外周血祖细胞在浓度高达100微摩尔时对TG具有高度抗性，而AML骨髓原代培养物在TG浓度>7.5微摩尔时活力显著下降。标准细胞毒性药物（柔红霉素、依托泊苷和阿糖胞苷）与TG联合使用在6种AML细胞系中具有协同作用，当在添加细胞毒性药物之前用TG预处理细胞24小时时，协同作用最强。在纳摩尔浓度的TG下可观察到细胞毒性药物的半数抑制浓度（IC50）显著下降。TG与AML治疗中使用的细胞毒性药物之间的体外协同作用为体内评估这些联合用药提供了依据。
