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

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。

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.