Down-regulation of lipocalin 2 suppresses the growth of human lung adenocarcinoma through oxidative stress involving Nrf2/HO-1 signaling.
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/heme 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.
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.
Baoquan
B
Song
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.
Hairui
H
Zhang
Department of Thoracic Surgery, the First Affiliated Hospital of Nanchang University, Nanchang 330000, China.
Lei
L
Jiang
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.
Ying
Y
Chi
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.
Jianjian
J
Tian
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.
Wenjing
W
Du
Department of Thoracic Surgery, the First Affiliated Hospital of Nanchang University, Nanchang 330000, China yubentong@126.com hanzhongchao@hotmail.com.
Bentong
B
Yu
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 yubentong@126.com hanzhongchao@hotmail.com.
Zhongchao
Z
Han
D000209:Acute-Phase Proteins / Q000378:metabolism*; D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
D000209:Acute-Phase Proteins; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D011518:Proto-Oncogene Proteins; D017382:Reactive Oxygen Species; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1
apoptosis; lung adenocarcinoma; neutrophil gelatinase-associated lipocalin; reactive oxygen species