罗格列酮通过PI3K/PTEN/Akt通路抑制人肝癌HepG2细胞增殖  

Rosiglitazone inhibits human HepG2 cell proliferation via PI3K/PTEN/Akt signaling pathway

作　　者：张萌[1] 彭利[1] 乔治斌[1] 何宏涛[1] 周烨[1] 徐卓[1] 

机构地区：[1]河北医科大学第四医院,河北石家庄050011

出　　处：《细胞与分子免疫学杂志》2014年第2期147-150,共4页Chinese Journal of Cellular and Molecular Immunology

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：目的研究罗格列酮对人肝癌HepG2细胞增殖与细胞周期的影响,通过检测相关蛋白的表达变化,探讨其可能机制。方法不同浓度罗格列酮作用于HepG2细胞,MTT法测定细胞增殖抑制率,流式细胞术检测细胞周期的变化,Western blot法检测PTEN、pAkt、S期激酶相关蛋白2(Skp2)及P27kip1蛋白表达变化,RT-PCR检测PTEN、Skp2及P27kip1mRNA表达变化。结果罗格列酮可明显抑制HepG2细胞的增殖,呈现时间和浓度依赖性(P<0.05);G0/G1期HepG2细胞比例明显升高,S期细胞比例明显降低(P<0.05)。Western blot结果显示罗格列酮可下调HepG2细胞中pAkt和Skp2蛋白的表达,上调PTEN和P27kip1蛋白表达(P<0.05)。RT-PCR结果显示罗格列酮可明显上调PTEN mRNA的表达,下调Skp2mRNA的表达,而P27kip1mRNA表达无明显变化。结论罗格列酮可抑制HepG2细胞的增殖,造成G0/G1期阻滞,其机制可能与罗格列酮经PI3K/PTEN/Akt信号通路参与Skp2及P27kip1蛋白的调控有关。Objective To investigate the effects of rosiglitazone （ROZ） on proliferation and cell cycle of human hepatocellular carcinoma call line HepG2 and explore the underlying mechanisms by detecting the related proteins. Methods After treated with ROZ of different concentrations, HepG2 cells were tested for the changes in the cell proliferation by Ml-r assay and in the cell cycle by flow cytometry. Western blotting and RT-PCR were performed to measure the expressions of PTEN, pAkt, S phase kinase associated protein 2 （Skp2） and P2^（kipl） at protein and mRNA levels, respectively. Res^dts ROZ significantly inhibited HepG2 cell proliferation in a concentration-dependent and time-dependent manner （P 〈 0.05）. The proportion of HepG2 cells in G0/G] phase increased, and that in S phase decreased significantly （P 〈 0. 05 ）. ROZ reduced the expressions of pAkt and Skp2, and raised the expressions of PTEN and P27^（kipl） in HepG2 cells （P〈0.05）. RT-PCR revealed that ROZ increased the expressions of PTEN mRNA, decreased the expressions of Skp2 mRNA, and had no effect on P27^（kipl） mRNA. Conclusion Our study demonstrated that ROZ could inhibit HepG2 cell proliferation and block G0/GI phase, the mechanisms may be related to the regulation on the expressions of Skp2 and P27k^（kipl）through the PI3K/PTEN/Akt signaling pathway.

关 键 词：罗格列酮 PTEN PI3K Akt信号通路 肝细胞癌 凋亡 S期激酶相关蛋白2 P27^(kipl) 

分 类 号：R735.7[医药卫生—肿瘤] Q255[医药卫生—临床医学]