Down-regulation of lipocalin 2 suppresses the growth of human lung adenocarcinoma through oxidative stress involving Nrf2/HO-1 signaling  

作　　者：Baoquan Song Hairui Zhang Lei Jiang Ying Chi Jianjian Tian Wenjing Du Bentong Yu Zhongchao Han 

机构地区：[1]State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China [2]Department of Thoracic Surgery, the First Affiliated Hospital of Nanchang University, Nanchang 330000, China

出　　处：《Acta Biochimica et Biophysica Sinica》2015年第10期805-814,共10页生物化学与生物物理学报（英文版）

基　　金：This work was supported by the grants from the National Natural Science Foundation of China （Nos. 81330015 and 31470951） and the National Basic Research Program of China （No. 2011CB964802）.

摘　　要：Lipocalin 2 （LCN2）, a multifunctional secretory protein known as neutrophil gelatinase-associated lipocalin （NGAL）, is expressed in a variety of cancers. However, little is known about the biological functions of NGAL in the development of lung adenocarcinoma. In the present study, we primarily found that NGAL expression was up-regulated in human lung adenocarcinoma tissues. Additionally, depletion of NGAL expression decreased the ability of cell proliferation and induced cell apoptosis. Furthermore, with the addition of N-acetylcysteine, a scavenger of reactive oxygen species （ROS）, it was found that NGAL depletion was sufficient to cause apoptosis of lung adenocarcinoma cells by generating ROS through the inhibition of the nuclear factor E2-related factor 2/heine oxygenase-1 anti-oxidant pathway. Finally, the effect of NGAL down-regulation on the growth of human lung adenocarcinoma was determined in BALB/c nude mice. These findings demonstrate that NGAL may be a potential therapy target for patients with lung adenocarcinoma.Lipocalin 2 （LCN2）, a multifunctional secretory protein known as neutrophil gelatinase-associated lipocalin （NGAL）, is expressed in a variety of cancers. However, little is known about the biological functions of NGAL in the development of lung adenocarcinoma. In the present study, we primarily found that NGAL expression was up-regulated in human lung adenocarcinoma tissues. Additionally, depletion of NGAL expression decreased the ability of cell proliferation and induced cell apoptosis. Furthermore, with the addition of N-acetylcysteine, a scavenger of reactive oxygen species （ROS）, it was found that NGAL depletion was sufficient to cause apoptosis of lung adenocarcinoma cells by generating ROS through the inhibition of the nuclear factor E2-related factor 2/heine oxygenase-1 anti-oxidant pathway. Finally, the effect of NGAL down-regulation on the growth of human lung adenocarcinoma was determined in BALB/c nude mice. These findings demonstrate that NGAL may be a potential therapy target for patients with lung adenocarcinoma.

关 键 词：neutrophil gelatinase-associated lipocalin lung adenocarcinoma apoptosis reactive oxygen species 

分 类 号：Q513[生物学—生物化学] Q753