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学科主题基础医学
Atorvastatin sensitizes human non-small cell lung carcinomas to carboplatin via suppression of AKT activation and upregulation of TIMP-1
Chen, Jie2,3; Lan, Tian4; Hou, Jincai1; Zhang, Jingjie2,3; An, Yu2,3; Tie, Lu2,3; Pan, Yan2,3; Liu, Jicheng1; Li, Xuejun2,3
关键词Atorvastatin Carboplatin AKT TIMP-1 Lung cancer
刊名INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
2012-05-01
DOI10.1016/j.biocel.2012.01.015
44期:5页:759-769
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology ; Cell Biology
研究领域[WOS]Biochemistry & Molecular Biology ; Cell Biology
关键词[WOS]COA REDUCTASE INHIBITORS ; OVARIAN-CANCER CELLS ; MATRIX METALLOPROTEINASES-1 ; SYNERGISTIC INHIBITION ; CISPLATIN RESISTANCE ; MAMMALIAN TARGET ; TISSUE INHIBITOR ; KINASE-B ; STATINS ; PATHWAY
英文摘要

Platinum-based chemotherapy is the standard treatment for advanced non-small-cell lung carcinomas (NSCLCs). However, the antitumoral effect of carboplatin displays unsatisfactory in NSCLCs treatment due to the AKT pathway-mediated carboplatin insensitive in NSCLCs treatment. Previous studies have shown that statins have antitumor activity, but it is unknown whether atorvastatin can reverse carboplatin resistance in lung cancer. Treatment with atorvastatin and carboplatin reduced the growth of xenograft A549 tumors in nude mice and enhanced the survival rate compared with carboplatin alone. Atorvastatin in combination with carboplatin had stronger effects on growth inhibition and apoptosis of NSCLC than either agent used individually. Carboplatin conferred anti-invasive effect in NSCLC cells mainly through inhibition of AKT activity and resultant upregulation of TIMP-1. However, the inhibitory effect on AKT activity by carboplatin was short-term. Additional atorvastatin administration resulted in synergistic inhibition of NSCLC cell invasion and stimulation of TIMP-1 expression with carboplatin through stronger and persistent inhibition of AKT activity both in vivo and in vitro. The synergy of atorvastatin and carboplatin was confirmed using another human lung carcinoma cell line (H1299). Altogether, our data demonstrate that atorvastatin may overcome carboplatin resistance in lung cancer by suppressing AKT activity and upregulating TIMP-1. A combination of atorvastatin and carboplatin may be an effective strategy in clinical therapy against NSCLCs. (c) 2012 Elsevier Ltd. All rights reserved.

语种英语
WOS记录号WOS:000303558600016
引用统计
被引频次:21[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/400002259/63900
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
4.Guangdong Pharmaceut Univ, Vasc Biol Res Inst, Guangzhou 510006, Guangdong, Peoples R China
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Chen, Jie,Lan, Tian,Hou, Jincai,et al. Atorvastatin sensitizes human non-small cell lung carcinomas to carboplatin via suppression of AKT activation and upregulation of TIMP-1[J]. INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY,2012,44(5):759-769.
APA Chen, Jie.,Lan, Tian.,Hou, Jincai.,Zhang, Jingjie.,An, Yu.,...&Li, Xuejun.(2012).Atorvastatin sensitizes human non-small cell lung carcinomas to carboplatin via suppression of AKT activation and upregulation of TIMP-1.INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY,44(5),759-769.
MLA Chen, Jie,et al."Atorvastatin sensitizes human non-small cell lung carcinomas to carboplatin via suppression of AKT activation and upregulation of TIMP-1".INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY 44.5(2012):759-769.
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