中文摘要：

目的：研究XN4在体外抑制急性粒细胞白血病细胞（ AML）增殖的作用与诱导DNA损伤的关系。方法 MTT法检测XN4对AML细胞增殖抑制作用；流式细胞术检测AML细胞反应性氧自由基（ ROS）、DNA损伤、细胞周期和细胞凋亡；Western blot探讨XN4对相关蛋白表达的影响。结果XN4明显抑制 AML 细胞增殖,半数抑制率（ IC50）分别为（2．79±0．15）μmol·L-1和（2．76±0．20）μmol·L-1；XN4增加细胞ROS水平和r-H2AX的表达,诱导细胞阻滞在S期并增加细胞凋亡率；XN4能增加H2AX、ATM的磷酸化以及Parp和 Caspase-3的切割,而减少 CDK2和 Cyclin E1的表达。结论 XN4通过激活ROS,诱导DNA的损伤和细胞周期S期阻滞,抑制 DNA损伤修复和诱导细胞的凋亡,抑制HL-60及KG1α细胞的增殖,抗氧化剂NAC （ N-乙酰半胱氨酸）能减少ROS的产生逆转XN4的作用。

英文摘要：

Aim To investigate the cytotoxicity of XN4 against AML cells, and the underlying mechanisms by which XN4 might induce DNA damage and apoptotic cell death through reactive oxygen species （ ROS ） . Methods The proliferation inhibition ratio of AML cells was measured by MTT. The level of extracellular ROS, DNA damage, cell cycle process and apoptosis were tested by flow cytometry （ FCM ） . Western blot was applied to test the expression of proteins. Results XN4 significantly inhibited the proliferation of HL-60 and KG1α with IC50 （ 2. 79 ＆#177; 0. 15 ） μmol ＆#183; L-1 and （2. 76 ＆#177; 0. 20） μmol＆#183;L-1 respectively. XN4 signifi-cantly increased the generation of intracellular ROS, followed by inducing DNA damage and activating the ATM-γ-H2AX signaling, which led to increases of cells in the S phases of the cell cycle. Subsequently, XN4 induced apoptotic cell death through activation of caspase-3 and Parp. Moreover, the above effects were all reversed by the ROS scavenger N-acetylcysteine （ NAC ） . Conclusion XN4-induced DNA damage and cell apoptosis in AML cells are mediated via ROS generation.