新型氮芥衍生物XHH诱导K562细胞凋亡的研究
Research on apoptosis of K562 cells induced by a novel nitrogen mustard derivative XHH
作者:苗久旺;张忠泉;张亚宏;李骞;赵瑾;谢松强;王超杰;
Author:
收稿日期: 年卷(期)页码:2012,27(01):-5-8
期刊名称:华西药学杂志
Journal Name:WEST CHINA JOURNAL OF PHARMACEUTICAL SCIENCES
关键字:氮芥衍生物;抗肿瘤;凋亡;Caspases
Key words:
基金项目:国家自然科学基金资助项目(批准号:20872027);;
国家重大研究计划培育项目(No.90913001);;
中国博士后科学基金(No.20090450092);;
河南省高等学校青年骨干教师资助计划(2009GGJS-022)
中文摘要
目的探讨新型氮芥衍生物N-[4-(二氯乙基)丁胺]-1,8-萘酰亚胺(XHH)对K562细胞的抗肿瘤作用及其机制。方法采用MTT法检测XHH对K562细胞增殖的影响;用Annexin V-FITC/Hoechst33342、PI/Hoechst33342和Rh123/Hoechst33342双染法高内涵观察细胞的形态学变化、凋亡率及线粒体膜电位;用分光光度法检测caspase-3、caspase-9的活性。结果在一定浓度范围内,XHH能抑制K562细胞的增殖且抗肿瘤活性优于美法仑,呈剂量和时间依赖性地诱导细胞凋亡、降低线粒体膜电位、活化caspase-3和caspase-9。结论 XHH具有较好的抗肿瘤活性,可通过线粒体/caspase-9/caspase-3途径诱导K562细胞凋亡。
参考文献
[1]Zhuang YY,Zhou CH,Wang YF,et al.Advances of nitrogen mus-tard compounds in antitumor agents[J].Chin pharm J,2008,43(17):1281-1287.
[2]Pain A,Samanta S,Dutta S,et al.Evaluation of naphthalmustine,a nitrogen mustard derivative of naphthalimide as a rationally-designed anticancer agent[J].J Exp Clin Cancer Res,2003,22(3):411-418.
[3]Wang N,Qu T,Shen LQ,et al.In-silico study of 4-methylsul-finyl-3-butenyl isothiocyanate binding to tubulin induces A549cells apoptosis[J].Acta pharm Sci,2010,45(7):934-939.
[4]Zhao WJ,Niu FL.Effect of trihydroxybenzoic acid dimmer on in-duction of apoptosis of HL-60 cells[J].Acta pharm Sin,2009,44(1):42-47.
[5]Liu TM,Zhu GZ,Zhou JS,et al.Lethal effect of benzene nitrogenmustard glucoside derivate on K562 cells[J].Chem Res ChinUniv,2008,24(6):762-766.
[6]Overbeeke R,Steffens-Nakken H,Vermes I,et al.Early fea-tures of apoptosis detected by four different flow cytometry assays[J].Apoptosis,1998,3(2):115-121.
[7]Xie SQ,Zhang ZQ,Hu GQ,et al.HL-37,a novel anthracenederivative,induces Ca2+-mediated apoptosis in human breastcancer cells[J].Toxicol,2008,254(1-2):68-74.
[8]Holl V,Coelho D,Silbernagel L,et al.Prevention of nitrogen mus-tard-induced apoptosis in normal and transformed lymphocytesby ebselen[J].Biochem Pharmacol,2000,60(11):1565-1577.
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