罗格列酮激活p38MAPK通路调控p53及p21影响人肝癌HepG2细胞周期  

Rosiglitazone induces cell cycle arrest in hepatocellular carcinoma cell line HepG2 via p38MAPK/p53/p21 pathway

作　　者：张萌[1] 彭利[1] 乔治斌[1] 何宏涛[1] 周烨[1] 

机构地区：[1]河北医科大学第四医院肝胆外科,石家庄050011

出　　处：《第三军医大学学报》2014年第3期240-243,共4页Journal of Third Military Medical University

基　　金：河北省高校强势特色学科资助项目(2005-52);河北省卫生厅资助课题(06142)~~

摘　　要：目的研究p38丝裂原活化蛋白激酶(p38MAPK)通路及相关蛋白在罗格列酮引发的人肝癌HepG2细胞周期阻滞过程中的作用。方法 MTT法检测罗格列酮对人肝癌HepG2细胞增殖的影响,流式细胞术检测细胞周期分布,Western blot检测p38MAPK通路相关蛋白的表达变化。结果罗格列酮可抑制HepG2细胞的增殖,并引发G0/G1期阻滞(P<0.05)。Western blot检测结果显示罗格列酮可激活p38MAPK通路,上调HepG2细胞中磷酸化p53蛋白及p21蛋白的表达水平(P<0.05);而ERK1/2及JNK的磷酸化程度没有明显变化。p38MAPK通路抑制剂SB203580可明显减弱罗格列酮对HepG2细胞的增殖抑制及周期阻滞作用;并且SB203580可部分逆转由罗格列酮引发的磷酸化p53及p21蛋白的表达变化。结论罗格列酮可通过激活p38MAPK通路引发人肝癌HepG2细胞周期阻滞,其机制可能与p38MAPK通路激活后参与对磷酸化p53蛋白及p21蛋白的调控有关。induced cell cycle Objective To explore the role of p38MAPK signaling pathway in rosiglitazone （ROZ） - arrest in human hepatocellular carcinoma cell line HepG2. Methods HepG2 cells were treated with different concentrations of ROZ. The proliferation inhibitory rates were analyzed by MTF assay. Cell cycle distributions were detected by flow cytometry （FCM）. Western blotting was used to detect the expression of proteins related to p38MAPK signaling HepG2 cells, and induced an increase in the pathway. Results ROZ significantly inhibited proliferation of percentage of G0/G1 phase cells and a decrease in the percentage of S phase cells accompanied by the change in DNA ploidy （P 〈0.05）. ROZ increased p38MAPK phosphorylation but not ERK1/2 or JNK phosphorylation, and up-regulated the protein expression levels of p-p53 and p21 in HepG2 cells （P 〈 0.05）. In addition, the ROZ-induced cell proliferation inhibition and cell cycle arrest were partly blocked by p38MAPK inhibitor SB203580, as well as the changes of p-p53 and p21 proteins. Conclu- sion ROZ inhibits cell proliferation and induces cell cycle arrest in G0/G1 stage of HepG2 ceils by the activa- tion of p38MAPK pathway, which may be mediated by the p38MAPK/p53/p21 signaling axis.

关 键 词：罗格列酮 肝细胞癌 细胞周期 P38丝裂原活化蛋白激酶 P53 P21 

分 类 号：R73-361[医药卫生—肿瘤] R730.23[医药卫生—临床医学]