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[博宁霉素诱导人肿瘤细胞衰老的特征]

[Characteristics of boningmycin induced cellular senescence of human tumor cells].

作者信息

Zhang Xiu-Min, Gao Ning, Chen Ru-Xian, Xu Hong-Zhang, He Qi-Yang

机构信息

Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.

出版信息

Yao Xue Xue Bao. 2010 May;45(5):589-94.

Abstract

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. MIT 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 micromol x 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.

摘要

细胞衰老 是对抗肿瘤的重要步骤之一。本研究旨在观察博宁霉素诱导人肿瘤细胞衰老的特征。采用MTT法和克隆形成试验检测其生长抑制作用。用衰老相关β-半乳糖苷酶染色检测细胞衰老。用流式细胞术分析细胞周期分布和细胞内活性氧(ROS)的积累。通过蛋白质印迹法检测蛋白质表达。结果表明,博宁霉素对人口腔上皮癌KB细胞的生长抑制作用明显强于对非小细胞肺癌A549细胞的作用。与阿霉素的类似作用相比,博宁霉素在两种细胞系中均诱导细胞衰老特征,这是由于细胞停滞在G2/M期和ROS水平升高所致。在0.1微摩尔×L(-1)剂量的博宁霉素处理后,分子衰老标记物P21显著增加,而更高浓度则诱导细胞凋亡。结果表明,博宁霉素诱导的细胞衰老 是其肿瘤抑制机制之一。

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