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新型氮芥衍生物XHH诱导K562细胞凋亡的研究
引用本文:苗久旺,张忠泉,张亚宏,李骞,赵瑾,谢松强,王超杰.新型氮芥衍生物XHH诱导K562细胞凋亡的研究[J].华西药学杂志,2012,27(1):5-8.
作者姓名:苗久旺  张忠泉  张亚宏  李骞  赵瑾  谢松强  王超杰
作者单位:1. 河南大学化学生物学研究所,河南开封475004;山东中医药高等专科学校药理学教研室,山东烟台264100
2. 河南大学化学生物学研究所,河南开封,475004
3. 河南省天然药物与免疫工程重点实验室,河南开封,475004
4. 河南大学化学生物学研究所,河南开封475004;河南省天然药物与免疫工程重点实验室,河南开封475004
基金项目:国家自然科学基金,国家重大研究计划培育项目,中国博士后科学基金,河南省高等学校青年骨干教师资助计划
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。

关 键 词:氮芥衍生物  抗肿瘤  凋亡  Caspases

Research on apoptosis of K562 cells induced by a novel nitrogen mustard derivative XHH
MIAO Jiu-wang , ZHANG Zhong-quan , ZHANG Ya-hong , LI Qian , ZHAO Jin , XIE Song-qiang , WANG Chao-jie.Research on apoptosis of K562 cells induced by a novel nitrogen mustard derivative XHH[J].West China Journal of Pharmaceutical Sciences,2012,27(1):5-8.
Authors:MIAO Jiu-wang  ZHANG Zhong-quan  ZHANG Ya-hong  LI Qian  ZHAO Jin  XIE Song-qiang  WANG Chao-jie
Institution:1.Institute of Chemical Biology,Henan University,Kaifeng,Henan,475004 P.R.China;2.Department of Pharmacology,Shandong college of Traditional Chinese Medicine,Yantai,Shandong,264100 P.R.China;3.The Key Laboratory of Natural Medicine and Immuno Engineering,Kaifeng,Henan,475004 P.R.China)
Abstract:OBJECTIVE To investigate the antitumor effects and its possible mechanisms of a novel nitrogen mustard derivative(XHH) on K562 cells.METHODS Cell proliferative effect was assessed by MTT assay.The changes of morphology,apoptotic rate and mitochondrial membrane potential(MMP) were assessed by AnnexinV-FITC/Hoechst33342,PI/Hoecsht33342 and Rh123/Hoechst33342 double staining using high content screening(HCS),respectively.The activation of caspase-3,caspase-9 was evaluated by spectrophotometric method.RESULTS XHH showed a better proliferation inhibition effection on K562 cells than Melphalan due to its induction of apoptosis in a dose-and time-dependent manner,reduction of MMP,and activation of caspase-3 and caspase-9.CONCLUSION XHH showed a nice antitumor activity,induced apoptosis of K562 cells via caspase-9/caspase-3 mitochondrial pathway.
Keywords:Nitrogen mustard derivative  Antitumor  Apoptosis  Caspases
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