中文摘要：

本研究探讨番荔枝内酯类聚醚类似物AA005广泛的体外抗白血病细胞增殖效应及对急性早幼粒白血病细胞系NB4的可能作用机制。采用CCK-8试剂盒检测AA005对多种白血病细胞系增殖的影响;台盼蓝染色法检测细胞活率的改变;瑞氏染色后显微镜观察NB4细胞形态学结构的变化;流式细胞术分析细胞死亡形式;WesternBlot检测caspase-3的活化情况及其底物PARP-1的剪切情况;流式细胞术检测低浓度AA005（〈200 nmol/L）对细胞周期的影响。结果表明,高浓度AA005（〉200 nmol/L）能够抑制多种白血病细胞的增殖,呈浓度依赖性;不同浓度的AA005作用于NB4、U937、K562白血病细胞48 h后,绝大多数细胞死亡;以NB4细胞为例,AA005作用后出现类似凋亡形态特征;AA005几乎可同时诱导细胞发生早期凋亡及晚期凋亡;AA005诱导细胞死亡过程中仅有微弱的caspase-3活化及其底物PARP-1的剪切,caspase广谱抑制剂Z-VAD-fmk不能抑制AA005所致的细胞死亡;非毒性浓度的AA005（〈200 nmol/L）引起细胞G2/M期阻滞。结论：番荔枝内酯类聚醚类似物AA005具有广泛的抗白血病细胞增殖效应,其机制可能与AA005诱导白血病细胞死亡及引起细胞G2/M期阻滞有关。

英文摘要：

This study was aimed to investigate the biological behavior of annonaceous acetogenin mimic AA005 in various kinds of leukemia cells and further elaborated its possible mechanisms in acute promyelocytic leukemia（APL） cell line NB4.The proliferative inhibition of leukemia cells was measured by CCK-8 method.Cell death was determined by trypan blue.Cell morphological features of NB4 treated with AA005 were examined by microscopy after Wright′s staining.The form of cell death was measured by flow cytometry.Proteins PARP-1 and caspase-3 were detected by Western blot.Flow cytometry was used to detect the cell cycle arrest induced by AA005 of low concentration.The results showed that AA005（〉200 nmol/L） significantly inhibited proliferation of all tested leukemia cell lines in a concentration-dependent manner.The vast majority of cells went to die after leukemia cell lines of NB4,U937 and K562 were treated with different concentration of AA005 for 48 h.Typical morphologic changes significantly appeared in NB4 cells after AA005 treatment.AA005 almost simultaneously induced early apoptosis and late apoptosis.The little cleavage of PARP-1 and activation of caspase-3 happened in AA005-induced cell death,and caspase-3 inhibitor Z-VAD-fmk could not block the cell death.The non-toxic concentrations of AA005（〈 200 nmol/L）caused NB4 cells G2/M-phase arrest.It is concluded that annonaceous acetogenin mimic AA005 induces significant proliferative inhibition of various leukemia cell lines in a concentration-dependent manner,which may be associated with cell death and G2/M-phase arrest induced by AA005.