多胺衍生物NNIspm诱导肝癌细胞HepG2衰老及其分子机制  

NNIspm,a polyamine derivative,induces cellular senescence of human hepatoma HepG2 cells and its molecular mechanism

作　　者：谢松强[1,2] 张亚宏[2] 卢慧芳[1,2] 申阿春[1,2] 李骞[2] 李景华[2] 赵瑾[2] 王超杰[2] 

机构地区：[1]河南大学化学生物学研究所,河南开封475004 [2]河南省天然药物与免疫工程重点实验室,河南开封475004

出　　处：《药学学报》2012年第3期405-408,258,共4页Acta Pharmaceutica Sinica

基　　金：国家重大研究计划培育项目(90913001);中国博士后科学基金资助项目(20090450092;201003395);河南省基础与前沿技术研究项目(102300410095);河南省高校青年骨干教师资助计划(2009GGJS-022)

摘　　要：探讨多胺衍生物NNIspm诱导肝癌细胞HepG2衰老及其分子机制。采用β-半乳糖苷酶染色检测细胞衰老;应用高内涵活细胞成像系统检测细胞内NNIspm含量,细胞周期分布以及细胞内活性氧水平;Western blotting检测蛋白的表达水平;应用高效液相色谱法检测细胞内多胺含量的变化。结果表明:NNIspm可明显诱导HepG2细胞发生衰老,这与其降低细胞内多胺含量,诱导细胞周期阻滞于G0/G1期、增加细胞内活性氧有关。此外,检测到衰老标志蛋白p21的表达明显增加;相反,Cyclin E和CDK2的表达明显减弱。本研究结果表明:NNIspm引起的细胞衰老是其产生抗肿瘤作用的机制之一。This study is to examine the effects of NNIspm-mediated cellular senescence of HepG2 cells and elucidate its potential molecular mechanism.Cellular senescence was detected with senescence-associated beta-galactosidase staining.Cell cycle distribution,intracellular fluorescence intensity and accumulation of intracellular reactive oxygen species（ROS） were detected by high content screening（HCS）.Protein expression was detected by Western blotting.Polyamines content was analyzed by high performance liquid chromatography（HPLC）.The results demonstrated that NNIspm significantly induced HepG2 cells senescence.This effect was due to the decrease of intracellular polyamines,the arrest at G0/G1 phase and an increase of ROS level.The molecular senescence marker p21 increased significantly after NNIspm treatment.In contrast,the protein expressions of Cyclin E and CDK2 were obvious down-regulation.The results indicated that cellular senescence induced by NNIspm was one of its antitumor mechanisms.

关 键 词：多胺衍生物 细胞衰老 多胺 抗肿瘤作用 

分 类 号：R963[医药卫生—微生物与生化药学]