Downregulation of Nrf2 promotes radiation-induced apoptosis through Nrf2 mediated Notch signaling in non-small cell lung cancer cells

doi:10.3892/ijo.2015.3301

	Downregulation of Nrf2 promotes radiation-induced apoptosis through Nrf2 mediated Notch signaling in non-small cell lung cancer cells
	Zhao, Qiuyue 1,2,3,4; Mao, Aihong 1,2,3,4; Yan, Jiawei 1,2,3,4; Sun, Chao 1,2,3; Di, Cuixia1,2,3 ; Zhou, Xin1,2,3 ; Li, Hongyan 1,2,3; Guo, Ruoshui 5; Zhang, Hong1,2,3
刊名	INTERNATIONAL JOURNAL OF ONCOLOGY
	2016-02-01
卷号	48 页码:765-773
关键词	nuclear factor erythroid-2-related factor 2 ionizing radiation ROS Notch1 lung cancer
ISSN号	1019-6439
DOI	10.3892/ijo.2015.3301
英文摘要	The nuclear factor erythroid-2-related factor 2 (Nrf2) is a crucial regulator of the cellular antioxidant system. Nrf2 is often constitutively activated in non-small cell lung cancer (NSCLC) cell lines, which promotes cytoprotection against oxidative stress and xenobiotics. Notch1 signaling is critically implicated in cell fate determination. It has been reported that Nf2 strongly regulates Notch1 activity. However, the role of Nrf2 mediated Notch1 signaling in response to ionizing radiation (IR) remains elusive. We report that knockdown of Nrf2 promotes radiation-induced apoptosis through Nrf2 mediated Notch1 signaling in NSCLC cells. IR activated Nrf2 in a dose-dependent manner and the expression of Nrf2 was significantly elevated at 4 h after exposure. RNAi-mediated reduction of Nrf2 significantly increased endogenous ROS levels, and decreased the expression of glutamate cysteine ligase catalytic subunit (GCLC), heme oxygenase-1 (HO-1) and NAD (P) H quinine oxidoreductase-1 (NQO1) in irradiated cells. Furthermore, decrease in Nrf2 expression significantly dampened Notch1 expression following ionizing radiation exposure, and potentiated IR-induced cellular apoptosis. These results demonstrated that Nrf2 could be activated by ionizing radiation, knockdown of Nrf2 could promote radiation induced apoptosis and Nrf2-mediated Notch signaling is an important determinant in radioresistance of lung cancer cells.
资助项目	Key Program of National Natural Science Foundation of China[U1432248] ; National Natural Science Foundation of China[11105203] ; National Natural Science Foundation of China[11305224]
WOS关键词	GENE-EXPRESSION ; HEPATOCELLULAR-CARCINOMA ; NRF2/KEAP1 PATHWAY ; SYSTEMIC-SCLEROSIS ; STEM-CELLS ; IN-VIVO ; ACTIVATION ; SURVIVAL ; RADIORESISTANCE ; GROWTH
WOS研究方向	Oncology
语种	英语
出版者	SPANDIDOS PUBL LTD
WOS记录号	WOS:000366897500033
资助机构	Key Program of National Natural Science Foundation of China ; National Natural Science Foundation of China
内容类型	期刊论文
源URL	[http://119.78.100.186/handle/113462/41274]
专题	中国科学院近代物理研究所
通讯作者	Zhang, Hong
作者单位	1.Chinese Acad Sci, Inst Modern Phys, Lanzhou 730000, Gansu, Peoples R China 2.Chinese Acad Sci, Key Lab Heavy Ion Radiat Med, Lanzhou 730000, Gansu, Peoples R China 3.Key Lab Heavy Ion Radiat Med Gansu Prov, Lanzhou 730000, Gansu, Peoples R China 4.Univ Chinese Acad Sci, Beijing 100039, Peoples R China 5.South China Agr Univ, Guangzhou 510642, Guangdong, Peoples R China
推荐引用方式 GB/T 7714	Zhao, Qiuyue,Mao, Aihong,Yan, Jiawei,et al. Downregulation of Nrf2 promotes radiation-induced apoptosis through Nrf2 mediated Notch signaling in non-small cell lung cancer cells[J]. INTERNATIONAL JOURNAL OF ONCOLOGY,2016,48:765-773.
APA	Zhao, Qiuyue.,Mao, Aihong.,Yan, Jiawei.,Sun, Chao.,Di, Cuixia.,...&Zhang, Hong.(2016).Downregulation of Nrf2 promotes radiation-induced apoptosis through Nrf2 mediated Notch signaling in non-small cell lung cancer cells.INTERNATIONAL JOURNAL OF ONCOLOGY,48,765-773.
MLA	Zhao, Qiuyue,et al."Downregulation of Nrf2 promotes radiation-induced apoptosis through Nrf2 mediated Notch signaling in non-small cell lung cancer cells".INTERNATIONAL JOURNAL OF ONCOLOGY 48(2016):765-773.