PE, a new sulfated saponin from sea cucumber, exhibits anti-angiogenic and anti-tumor activities in vitro and in vivo

doi:10.4161/cbt.4.8.1917

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第一研究室

	PE, a new sulfated saponin from sea cucumber, exhibits anti-angiogenic and anti-tumor activities in vitro and in vivo
	Tian, F ; Zhang, XW ; Tong, YG ; Yi, Y ; Zhang, SL ; Li, L; Sun, P ; Lin, LP ; Ding, J
刊名	CANCER BIOLOGY & THERAPY
	2005-08
卷号	4 期号:8 页码:874-882
关键词	PE marine angiogenesis endothelial cells VEGFR2 apoptosis anti-tumor
ISSN号	1538-4047
DOI	10.4161/cbt.4.8.1917
文献子类	Article
英文摘要	Here, we examined the in vitro and in vivo anti-angiogenesis and anti-tumor activities of PE, a new marine-derived compound. Inhibition of angiogenesis was assessed in vitro using proliferation, migration, adhesion, tube-formation and apoptosis assays in PE-treated HMECs and HUVECs. In vivo, CAM assays were used to assess inhibition effect of PE on physiological angiogenesis, and immunofluorescent microscopy was used to examine tumor microvessel density and apoptosis in PE-treated mouse tumor models. Finally, Western blotting analyses were performed to examine the effect of PE on VEGF signaling in HMECs. The results showed that PE inhibited proliferation of HMECs and HUVECs with IC(50)values of 2.22 +/- 0.31 mu M and 1.98 +/- 0.32 mu M, induced endothelial cell apoptosis at concentrations < 2 mu M, induced dose-dependent suppression of cell migration, cell adhesion and tube formation in HMECs and HUVECs, and showed anti-proliferative activities against several tumor cell lines (IC(50)values of similar to 4 mu M). In vivo, PE (5 nM/egg) suppressed spontaneous angiogenesis in our CAM assay, and induced marked growth inhibition in mouse sarcoma 180 and hepatoma 22 models. Specifically, PE treatment reduced mouse sarcoma 180 tumor volume by triggering apoptosis of both tumor and tumor-associated endothelial cells, preferentially targeting on endothelial cells comparable with tumor cells. Finally, PE treatment suppressed the active (phosphorylated) forms of VEGFR2, Akt, ERK, FAK and paxillin, which are involved in endothelial cell survival, proliferation, adhesion and migration. Our results indicate that PE exerts an anti-angiogenic activity associated with inhibition of VEGFR2 signaling, and an anti-tumor activity associated with decreased proliferation of tumor cells and increased apoptosis of both endothelial cells and tumor cells.
WOS关键词	ENDOTHELIAL GROWTH-FACTOR ; TUMOR ANGIOGENESIS ; NATURAL-PRODUCTS ; CANCER ; CELLS ; RECEPTOR ; KINASE ; CHEMOTHERAPY ; INHIBITION ; MECHANISM
WOS研究方向	Oncology
语种	英语
出版者	LANDES BIOSCIENCE
WOS记录号	WOS:000236043200024
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/273826]
专题	药理学第一研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Ding, J
作者单位	1.Second Mil Med Univ, Sch Pharm, Res Ctr Marine Drugs, Shanghai 200433, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, State Key Lab Drug Res,Div Anti Tumor Pharmacol, Shanghai 201203, Peoples R China 3.Chinese Acad Sci, Grad Sch, Beijing, Peoples R China
推荐引用方式 GB/T 7714	Tian, F,Zhang, XW,Tong, YG,et al. PE, a new sulfated saponin from sea cucumber, exhibits anti-angiogenic and anti-tumor activities in vitro and in vivo[J]. CANCER BIOLOGY & THERAPY,2005,4(8):874-882.
APA	Tian, F.,Zhang, XW.,Tong, YG.,Yi, Y.,Zhang, SL.,...&Ding, J.(2005).PE, a new sulfated saponin from sea cucumber, exhibits anti-angiogenic and anti-tumor activities in vitro and in vivo.CANCER BIOLOGY & THERAPY,4(8),874-882.
MLA	Tian, F,et al."PE, a new sulfated saponin from sea cucumber, exhibits anti-angiogenic and anti-tumor activities in vitro and in vivo".CANCER BIOLOGY & THERAPY 4.8(2005):874-882.