博宁霉素引起肿瘤细胞衰老的特征  

Characteristics of boningmycin induced cellular senescence of human tumor cells

作　　者：张秀敏[1] 高宁[1] 陈汝贤[1] 许鸿章[1] 何琪杨[1] 

机构地区：[1]中国医学科学院、北京协和医学院医药生物技术研究所,北京100050

出　　处：《药学学报》2010年第5期589-594,共6页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(30772284);科技部“重大新药创制”综合性大平台项目(2009ZX09301-003)

摘　　要：鉴于细胞衰老是抑制肿瘤的重要步骤,考察博宁霉素引起人肿瘤细胞衰老的特征。采用MTT法和克隆形成率实验检测细胞增殖抑制作用;衰老相关的β-半乳糖苷酶染色检测细胞衰老;流式细胞仪测定细胞周期分布以及细胞内活性氧自由基水平;Western blotting检测蛋白的表达水平。结果表明,博宁霉素对人口腔上皮癌KB细胞的作用,明显强于人非小细胞肺癌A549细胞。与阳性对照药多柔比星的作用相似,博宁霉素可引起这两种细胞均出现衰老特征,这与细胞阻滞在G2/M期、细胞内活性氧自由基增加有关。0.1μmol·L-1博宁霉素可以诱导KB细胞衰老,检测到衰老标志蛋白P21的表达明显增加;而高浓度的博宁霉素激活细胞凋亡通路。本研究结果表明:博宁霉素引起细胞衰老,也是其抑制肿瘤细胞增殖的机制之一。Cellular senescence is one of the important steps against tumor.This study was to observe the characteristics of boningmycin induced senescence of human tumor cells.MTT method and clone formation assay were used to detect the growth-inhibitory effect.Cellular senescence was detected with senescence-associated beta-galactosidase staining.Cell cycle distribution and accumulation of intracellular reactive oxygen species （ROS） were analyzed with flow cytometry.Protein expression was detected by Western blotting.The results showed that the growth-inhibitory effect of boningmycin was obviously stronger on human oral epithelial carcinoma KB cells than that on non-small cell lung cancer A549 cells.Comparison to the similar action of doxorubicin,that boningmycin induced the features of cellular senescence in both cell lines,its due to the arrest at G2/M phase and an increase of ROS level.The molecular senescence marker P21 increased significantly after boningmycin treatment at a dosage of 0.1 μmol·L^-1,whereas a higher concentration of it induced apoptosis.The results indicated that cellular senescence induced by boningmycin was one of its mechanisms in tumor suppression.

关 键 词：博宁霉素 博莱霉素族 细胞衰老 细胞凋亡 抗肿瘤作用 

分 类 号：R963[医药卫生—微生物与生化药学] R979.14[医药卫生—药理学]