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学科主题: 基础医学
题名:
Atorvastatin synergizes with IFN-gamma in treating human non-small cell lung carcinomas via potent inhibition of RhoA activity
作者: Chen, Jie2,3; Hou, Jincai1; Zhang, Jingjie2,3; An, Yu2,3; Zhang, Xiaojie1; Yue, Liling1; Liu, Jicheng1; Li, Xuejun2,3
关键词: IFN-gamma ; Non-small-cell-lung carcinomas ; NSCLCs ; RhoA ; Atorvastatin
刊名: EUROPEAN JOURNAL OF PHARMACOLOGY
发表日期: 2012-05-05
DOI: 10.1016/j.ejphar.2012.02.015
卷: 682, 期:1-3, 页:161-170
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Pharmacology & Pharmacy
研究领域[WOS]: Pharmacology & Pharmacy
关键词[WOS]: RECOMBINANT INTERFERON-GAMMA ; CLASS-I ANTIGENS ; MHC CLASS-I ; IMMUNE SURVEILLANCE ; DENDRITIC CELLS ; GROWTH ARREST ; CANCER CELLS ; EXPRESSION ; APOPTOSIS ; ACTIVATION
英文摘要:

Interferon-gamma (IFN-gamma) has been widely used to treat various malignant tumors including human non-small-cell-lung carcinomas (NSCLCs). However, the tumor-inhibitory effect of IFN-gamma displays not satisfactory in NSCLC treatment due to the lack of immunogenicity of NSCLCs. This study demonstrated that inhibition of RhoA activity led to significant inhibition of NSCLC cell growth accompanied by decreased expression of c-myc and cyclin D1 and increased levels of major histocompatibility complex (MHC) class land peptide transporter protein 1 (TAP1) which are involved in tumor immunity. Combination treatment of atorvastatin and IFN-gamma resulted in a synergistic inhibition of NSCLC cell growth both in vitro and in vivo. Though IFN-gamma alone exerted minimal inhibitory effect on RhoA activity, additional administration of atorvastatin could result in a significant inhibition of RhoA activity, thus substantially suppressing NSCLC cell growth. Specifically, atorvastatin could induce specific deposition of endogenous IFN-gamma in tumors while not in other normal tissues in LLC-harbored mice. In conclusion, atorvastatin can enhance IFN-gamma sensitivity in NSCLCs both in vitro and in vivo, probably through induction of a synergistic inhibitory effect on RhoA activity. This study also suggests a potential alternative of combination of atorvastatin and IFN-gamma in clinical therapy against NSCLCs. (C) 2012 Elsevier B.V. All rights reserved.

语种: 英语
所属项目编号: 81020108031 ; 30572202 ; 30973558 ; 30772571 ; 30901815 ; 30901803 ; 30973902 ; 2009ZX09103-144 ; B07001 ; D200929
项目资助者: National Natural Science Foundation of China ; Ministry of Science and Technology in China ; Ministry of Education of China (111) ; Province Natural Science Foundation of Hei Long Jiang
WOS记录号: WOS:000302982400022
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/67395
Appears in Collections:基础医学院_药理学系_期刊论文

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作者单位: 1.Peking Univ, Inst Syst Biomed, Beijing 100191, Peoples R China
2.Qi Qi Ha Er Med Univ, Med & Drug Res Inst, Hei Long Jiang 161009, Peoples R China
3.Peking Univ, State Key Lab Nat & Biomimet Drugs, Dept Pharmacol, Sch Basic Med Sci, Beijing 100191, Peoples R China

Recommended Citation:
Chen, Jie,Hou, Jincai,Zhang, Jingjie,et al. Atorvastatin synergizes with IFN-gamma in treating human non-small cell lung carcinomas via potent inhibition of RhoA activity[J]. EUROPEAN JOURNAL OF PHARMACOLOGY,2012,682(1-3):161-170.
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