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学科主题基础医学
Curcumin inhibits tumor proliferation induced by neutrophil elastase through the upregulation of alpha 1-antitrypsin in lung cancer
Xu, Yan1,2; Zhang, Jingjie1,2; Han, Jing1,2; Pan, Xueyang1,2; Cao, Yajun1,2,3; Guo, Hao1,2; Pan, Yan1,2; An, Yu1,2; Li, Xuejun1,2
关键词Curcumin Tumor Proliferation Alpha 1-antitrypsin Neutrophil Elastase
刊名MOLECULAR ONCOLOGY
2012-08-01
DOI10.1016/j.molonc.2012.03.005
6期:4页:405-417
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology
研究领域[WOS]Oncology
关键词[WOS]FACTOR-KAPPA-B ; NONSMALL CELL LUNG ; PANCREATIC-CANCER ; OVARIAN-CANCER ; ANGIOGENESIS ; APOPTOSIS ; INFLAMMATION ; CARCINOMA ; MECHANISM ; GENE
英文摘要

Lung carcinogenesis is a complex process in an unregulated inflammatory environment. Curcumin has been extensively investigated as a multi-target anti-tumor and anti-inflammation compound. In this paper, we demonstrate a novel inflammation-related mechanism for curcumin-induced inhibition of lung tumor growth. We found that neutrophil elastase, an important regulator of inflammatory processes, directly triggered tumor cell proliferation in human lung adenocarcinoma A549 cells, and curcumin could completely suppress the excess tumor proliferation induced by neutrophil elastase. alpha 1-antitrypsin is synthesized by tumor cells and is the natural inhibitor of neutrophil elastase. We found that curcumin counteracted the decrease of alpha 1-antitrypsin induced by neutrophil elastase by inducing the promoter activity of alpha 1-antitrypsin and promoting its expression in A549 cells. The inhibition of neutrophil elastase-induced proliferation by curcumin was dependent on the PI3K/Akt pathway. Knockdown of alpha 1-antitrypsin by siRNA further enhanced the tumor cell proliferation induced by neutrophil elastase and significantly blocked the anti-proliferation effect of curcumin against neutrophil elastase. Curcumin remarkably inhibited the primary tumor growth of Lewis lung carcinoma (LLC) in C57BL/6 mice. We further showed that curcumin upregulated the level of alpha 1-antitrypsin in primary tumor tissue by promoting its local expression, and the protein level of neutrophil elastase in tumor tissue was obviously decreased in mice treated with curcumin. Overall, our results suggest that neutrophil elastase and alpha 1-antitrypsin play important roles in modulating lung tumor proliferation in inflammatory microenvironment and curcumin inhibits neutrophil elastase-induced tumor proliferation via upregulating alpha 1-antitrypsin expression in vitro and in vivo. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

语种英语
WOS记录号WOS:000307531200003
项目编号81020108031 ; 30572202 ; 30973558 ; 91129727 ; 30901815 ; 30901803 ; 2009ZX09103-144 ; B07001
资助机构National Natural Science Foundation of China ; Major Specialized Research Fund from the Ministry of Science and Technology in China ; Research Fund from Ministry of Education of China
引用统计
被引频次:32[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/400002259/57432
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.Peking Univ, State Key Lab Nat & Biomimet Drugs, Dept Pharmacol, Sch Basic Med Sci, Beijing 100191, Peoples R China
3.Shihezi Univ, Key Lab Xinjiang Phytomed Resources Modernizat TC, Sch Pharmaceut Sci, Shihezi 832002, Xinjiang, Peoples R China
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GB/T 7714
Xu, Yan,Zhang, Jingjie,Han, Jing,et al. Curcumin inhibits tumor proliferation induced by neutrophil elastase through the upregulation of alpha 1-antitrypsin in lung cancer[J]. MOLECULAR ONCOLOGY,2012,6(4):405-417.
APA Xu, Yan.,Zhang, Jingjie.,Han, Jing.,Pan, Xueyang.,Cao, Yajun.,...&Li, Xuejun.(2012).Curcumin inhibits tumor proliferation induced by neutrophil elastase through the upregulation of alpha 1-antitrypsin in lung cancer.MOLECULAR ONCOLOGY,6(4),405-417.
MLA Xu, Yan,et al."Curcumin inhibits tumor proliferation induced by neutrophil elastase through the upregulation of alpha 1-antitrypsin in lung cancer".MOLECULAR ONCOLOGY 6.4(2012):405-417.
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