彪马
细胞凋亡
基因敲除
下调和上调
阿霉素
化学
MTT法
标记法
转染
分子生物学
MAPK/ERK通路
生物
细胞生物学
细胞培养
信号转导
生物化学
化疗
基因
遗传学
作者
Zhang Dx,Ma Dy,Yao Zq,Fu Cy,Shi Yx,Wang Ql,Tang Qq
出处
期刊:PubMed
日期:2016-06-01
卷期号:20 (11): 2435-42
被引量:21
摘要
Numerous studies have demonstrated that Doxorubicin (DOX) induces cardiomyocyte apoptosis, which is associated with DOX-induced acute and chronic cardiotoxicity. DOX activated ERP1/2 and NF-KB signals has been linked to DOX-induced apoptosis and cardiotoxicity. However, the underlying mechanisms responsible for DOX-induced apoptosis have not been completely elucidated. In this study, we determine whether both ERK1/2/p53-dependent and NF-κB dependent-PUMA activation was related to DOX-induced apoptosis in H9c2 cells.H9c2 cells were treated with DOX (1 μM) for 2-48 hours. To explore the effect of ERK1/2, NF-KB, P53 and PUMA on DOX-induced apoptosis in H9c2 cells, H9c2 cells were transfected with PUMA siRNA or p65 siRNA, or treated with PFT-α (a chemical inhibitor of p53), or PD98059 (ERK inhibitor) before DOX treatment. MTT, Flow cytometry, TUNEL, Western blot and EMSA assay was used to detect cell survival, apoptosis, protein expression and NF-KB activity.DOX induced apoptosis and inhibited growth of H9c2 cells in a time-dependent manner. DOX activated ERK1/2, NF-KB, p53 and PUMA. Knockdown of PUMA completely blocked DOX-induced cell apoptosis and survival inhibition. Knockdown of NF-KB or ERK1/2 alone could partly block DOX-induced PUMA upregulation and cell apoptosis. However, knockdown of NF-KB and ERK1/2 together completely blocked DOX-induced cell apoptosis and PUMA upregulation. In addition, knockdown of ERK1/2 blocked p53-dependent PUMA upregulation.DOX induced apoptosis and inhibited growth of H9c2 cells by activation of ERK1/2/p53 and NF-κB dependent-PUMA signaling pathway.
科研通智能强力驱动
Strongly Powered by AbleSci AI