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学科主题基础医学
Atorvastatin synergizes with IFN-gamma in treating human non-small cell lung carcinomas via potent inhibition of RhoA activity
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
2012-05-05
DOI10.1016/j.ejphar.2012.02.015
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
WOS记录号WOS:000302982400022
项目编号81020108031 ; 30572202 ; 30973558 ; 30772571 ; 30901815 ; 30901803 ; 30973902 ; 2009ZX09103-144 ; B07001 ; D200929
资助机构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
引用统计
被引频次:6[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/67395
专题北京大学基础医学院_药理学系
北京大学医学部管理机构_医学部
北京大学基础医学院
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
推荐引用方式
GB/T 7714
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.
APA Chen, Jie.,Hou, Jincai.,Zhang, Jingjie.,An, Yu.,Zhang, Xiaojie.,...&Li, Xuejun.(2012).Atorvastatin synergizes with IFN-gamma in treating human non-small cell lung carcinomas via potent inhibition of RhoA activity.EUROPEAN JOURNAL OF PHARMACOLOGY,682(1-3),161-170.
MLA Chen, Jie,et al."Atorvastatin synergizes with IFN-gamma in treating human non-small cell lung carcinomas via potent inhibition of RhoA activity".EUROPEAN JOURNAL OF PHARMACOLOGY 682.1-3(2012):161-170.
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