4-isothiocyanate-2, 2, 6, 6-tetramethyl piperidinooxyl inhibits angiogenesis by suppressing VEGFR2 and Tie2 phosphorylation

doi:10.3892/ol.2016.4948

	4-isothiocyanate-2, 2, 6, 6-tetramethyl piperidinooxyl inhibits angiogenesis by suppressing VEGFR2 and Tie2 phosphorylation
	Liu, Yuanyuan1,2 ; Gao, Jing 3; Huang, Shuangsheng 3; Hu, Lamei 1; Wang, Zhiqiang 1; Wang, Zheyuan 4; Chen, Xiao 4; Zhang, Xiaoyu 1; Li, Wenguang 1
刊名	ONCOLOGY LETTERS
	2016-10-01
卷号	12 页码:2828-2834
关键词	4-isothiocyanate-2 2 6 6-tetramethyl piperidinooxyl angiogenesis reactive oxygen species vascular endothelial growth factor receptor 2 Tie2
ISSN号	1792-1074
DOI	10.3892/ol.2016.4948
英文摘要	Reactive oxygen species (ROS) are involved in the signaling pathway and are triggered by angiogenic factors, including vascular endothelial growth factor and angiopoietins. 4-isothiocyanate-2, 2, 6, 6-tetramethyl piperidinooxyl (4-ISO-Tempo) is one of the nitroxides that exhibits antioxidant activity. However, the anti-angiogenic effect of 4-ISO-Tempo remains unknown. The aim of this study was to investigate the effect of 4-ISO-Tempo on tumor proliferation and angiogenesis as well as its underlying mechanisms. Our results revealed that 4-ISO-Tempo significantly inhibited the viability of neoplastic and endothelial cells. Furthermore, the effective concentration of 4-ISO-Tempo on human microvascular endothelial cell 1 (HMEC-1) was lower than that on human lung adenocarcinoma A549 and human colon cancer SW620 cells. This suggested that endothelial cells were more sensitive to 4-ISO-Tempo than tumor cells. Furthermore, we demonstrated that 4-ISO-Tempo also suppressed secretion of matrix metalloproteinase (MMP)-2 and MMP-9, and migration and tube formation of HMEC-1 cells. The mechanism is attributed to the decreasing ROS generation and further phosphorylation of vascular endothelial growth factor receptor 2 and Tie2. Our findings suggest that 4-ISO-Tempo should be investigated for its usefulness in anti-angiogenesis therapies.
资助项目	Medical Foundation of Lanzhou University[LZUYX200617] ; Key Lab of Preclinical Study for New Drugs of Gansu Province[GSKFKT-0702] ; National Natural Science Foundation of China[30700142]
WOS关键词	ENDOTHELIAL GROWTH-FACTOR ; NADPH OXIDASE 4 ; SIGNALING PATHWAYS ; PROSTATE-CANCER ; DOWN-REGULATION ; TUMOR-GROWTH ; IN-VIVO ; EXPRESSION ; RECEPTORS ; CELLS
WOS研究方向	Oncology
语种	英语
出版者	SPANDIDOS PUBL LTD
WOS记录号	WOS:000385579200091
资助机构	Medical Foundation of Lanzhou University ; Key Lab of Preclinical Study for New Drugs of Gansu Province ; National Natural Science Foundation of China
内容类型	期刊论文
源URL	[http://119.78.100.186/handle/113462/43475]
专题	中国科学院近代物理研究所
通讯作者	Li, Wenguang
作者单位	1.Lanzhou Univ, Coll Basic Med, Key Lab Preclin Study New Drugs Gansu, 199 Donggang West Rd, Lanzhou 730000, Gansu, Peoples R China 2.Chinese Acad Sci, Inst Modern Phys, Lanzhou 730000, Gansu, Peoples R China 3.Northwest Univ Nationalities, Clin Lab, Coll Med, Affiliated Hosp, Lanzhou 730030, Gansu, Peoples R China 4.Lanzhou Univ, Dept Gen Surg, Hosp 3, Lanzhou 730030, Gansu, Peoples R China
推荐引用方式 GB/T 7714	Liu, Yuanyuan,Gao, Jing,Huang, Shuangsheng,et al. 4-isothiocyanate-2, 2, 6, 6-tetramethyl piperidinooxyl inhibits angiogenesis by suppressing VEGFR2 and Tie2 phosphorylation[J]. ONCOLOGY LETTERS,2016,12:2828-2834.
APA	Liu, Yuanyuan.,Gao, Jing.,Huang, Shuangsheng.,Hu, Lamei.,Wang, Zhiqiang.,...&Li, Wenguang.(2016).4-isothiocyanate-2, 2, 6, 6-tetramethyl piperidinooxyl inhibits angiogenesis by suppressing VEGFR2 and Tie2 phosphorylation.ONCOLOGY LETTERS,12,2828-2834.
MLA	Liu, Yuanyuan,et al."4-isothiocyanate-2, 2, 6, 6-tetramethyl piperidinooxyl inhibits angiogenesis by suppressing VEGFR2 and Tie2 phosphorylation".ONCOLOGY LETTERS 12(2016):2828-2834.