三氮唑席夫碱衍生物诱导SMMC-7721细胞凋亡和裂亡  

Induction of apoptosis and mitotic catastrophe of hepatocarcinoma SMMC-7721 cells by triazole Schiff base derivative

作　　者：皇甫超申[1] 刘彬[1] 马永超[1] 胡国强[2] 

机构地区：[1]河南大学神经生物学研究所,河南开封475004 [2]河南大学药物研究所,河南开封475004

出　　处：《第四军医大学学报》2008年第11期998-1001,共4页Journal of the Fourth Military Medical University

基　　金：河南省科技攻关项目(124170229)

摘　　要：目的:研究三氮唑席夫碱衍生物体外诱导肝癌细胞凋亡和裂亡作用.方法:以不同剂量的3-吡啶-3-基-4-[(4-羟基-3-甲氧基-苯亚甲基)氨基]-5-甲硫基-1,2,4-三唑(LH-37)与SMMC-7721细胞共同培养,以MTT法测定细胞增殖,流式细胞术和荧光显微镜检测凋亡和细胞裂亡,免疫荧光观察微管骨架改变.结果:LH-37体外抑制肝癌细胞生长,抑制率呈浓度依赖性,药物作用48hIC50为2.0×10-4mol/L,不同的药物浓度诱导细胞凋亡情况有差别,1.0×10-4mol/L凋亡细胞明显增加,微管高度聚合,1.0×10-5mol/L组凋亡较少,药物作用72h,多倍体细胞明显增加,可见染色体异常凝集、异常有丝分裂、细胞核呈微核或碎核、微管明显聚合.结论:三氮唑席夫碱衍生物通过破坏微管诱导细胞凋亡、裂亡、抑制人肝癌细胞增殖.AIM： To study the effect of 3-pyridin-3-yl-4- [ （ 4- hydroxy-3-methoxy-benzylidene） amino ] -5-methylsulfanyl-4H-[ 1, 2,4] triazole （LH-37） on induction of apoptosis and mitotic catastrophe in hepatocarcinoma SMMC-7721. METHODS： Human hepatoma SMMC-7721 cell growth was measured by MTT- microculture tetrazolium assay. Apoptosis and mitotic catastrophe were analyzed by flow cytometry and fluorescence microscopic examination. Antitubulin antibody revealed a microtubular cytoskeleton consisting of cytoplasmic and spindle microtubules by immunofluorescence. RESULTS： LH-37 inhibited the hepatoma cell proliferation in a concentration dependent manner with IC50 at 2.0 × 10^-4 mol/L for 48 h. LH-37 at different doses induced a large variation in cell apoptosis. Treatment with 1.0 × 10 ^-4 mol/L LH-37 significantly increased cell apoptosis as well as polymerized microtubules. In SMMC-7721 cells exposed for 72 h to 1.0× 10^-5 mol/L triazole Schiff base derivative, the proportion of pelyploid cells was elevated significantly and the spontaneous chromosome condensation, abnormal mitosis, micronuclei and nuclear segments, polymerized microtubules were observed in these cells. CONCLUSION： LH-37 inhibits the proliferation of human hepatoma SMMC-7721 cells in vitro by damaging microtubule and agent causing apoptosis and mitotic catastrophe.

关 键 词：三氮唑席夫碱衍生物 人肝癌细胞 凋亡 裂亡 微管 

分 类 号：R735.7[医药卫生—肿瘤]