N-4-(二氯乙基)丁胺-1,8-萘酰亚胺对人肝癌HepG2细胞的抑制作用及其机制研究  

Inhibition effect and mechanism of novel nitrogen mustard derivative 2-( 4-di( 2-chloroethyl) aminobutylamino)-1H-benz-[de]isoquinoline-1,3(2H)-dione on human hepatoma HepG2 cells

作　　者：苗久旺[1,2,3] 张忠泉[1] 谢松强[1] 

机构地区：[1]河南大学化学生物学研究所,河南开封475004 [2]山东中医药大学药学院,济南250355 [3]山东中医药高等专科学校药理教研室,山东烟台264199

出　　处：《中国临床药理学杂志》2015年第20期2031-2033,共3页The Chinese Journal of Clinical Pharmacology

摘　　要：目的体外评价N-4-(二氯乙基)丁胺-1,8-萘酰亚胺(XHH)对Hep G2细胞的抑制作用及其作用机制。方法采用MTT法检测细胞增殖,高内涵筛选分析仪结合Annexin V-FITC/Hoechst33342,PI/Hoechst33342和Rh123/Hoechst33342双染色法检测细胞形态及膜电位;免疫荧光法检测caspase-3,caspase-9,Bcl-2,Bax的表达水平。结果 XHH能抑制Hep G2细胞增殖,诱导细胞凋亡,降低线粒体膜电位,提高Bax/Bcl-2,使caspase-3,caspase-9表达增加。结论 XHH具有较好的抗Hep G2肿瘤细胞作用,可通过线粒体途径诱导细胞凋亡。Objective To investigate the effects of 2 - （4 - di （ 2 - chlo- roethyl） aminobutylamino） - 1 H -benz - [ de ] isoquinoline - 1,3 （2H） -dione（XHH） , a novel nitrogen mustard derivative, on the growth and apoptosis in human hepatoma HepG2 cells in vitro. Methods Cell pro- liferative effect was assessed by MTF assay. Changes of morphology and mitochondrial membrane potential （MMP） were assessed by AnnexinV - FITC/Hoechst33342, PI/Hoecsht33342 and Rh123/Hoechst33342 double staining using high content screening （HCS）. The expression of caspase- 3, caspase- 9, Bcl -2, Bax was assessed by immunofluores- cence method using HCS. Results The resuhs indicated that XHH could inhibit the proliferation of HepG2 cells, induce apoptosis, lose MMP, up - regulate the ratio of Bax/Bcl - 2, increase the expression of caspase - 3, caspase - 9. Conclusion XHH could inhibit proliferative of human hepatoma HepG2 cells and induce cell apoptosis via mitochon- drial pathway.

关 键 词：氮芥衍生物 抗肿瘤 凋亡 CASPASE 

分 类 号：R963[医药卫生—微生物与生化药学] R979.1[医药卫生—药理学]