期刊
ONCOLOGY LETTERS
卷 12, 期 4, 页码 2828-2834出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/ol.2016.4948
关键词
4-isothiocyanate-2; 2; 6; 6-tetramethyl piperidinooxyl; angiogenesis; reactive oxygen species; vascular endothelial growth factor receptor 2; Tie2
类别
资金
- 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]
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.
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