Inhibition of trichostatin A-induced antiangiogenesis by small-interfering RNA for thrombospondin-1
Experimental & Molecular Medicine
;
: 402-411, 2007.
Article
in English
| WPRIM
| ID: wpr-195953
ABSTRACT
Expression of thrombospondin-1 (TSP-1), which is a known inhibitor of tumor growth and angiogenesis, is reciprocally regulated by positive regulators, such as VEGF. Additionally, trichostatin A (TSA) suppresses tumor progression by altering VEGF levels and VEGF-mediated signaling. Thus, understanding TSA-regulated TSP-1 expression and the effects of altered TSP-1 levels might provide insights into the mechanism of action of TSA in anti-tumorigenesis, and provide an approach to cancer therapy. Here, we examined the effect of TSA on TSP-1 expression, and the effects of TSA-induced TSP-1 on cell motility and angiogenesis, in HeLa and bovine aortic endothelial cells. TSA remarkably increased TSP-1 expression at the mRNA and protein levels, by controlling the TSP-1 promoter activity. Both TSA and exogenous TSP-1 reduced cell migration and capillary-like tube formation and these activities were confirmed by blocking TSP-1 with its neutralizing antibody and small-interfering RNA. Our results suggest that TSP-1 is a potent mediator of TSA-induced anti- angiogenesis.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
RNA, Messenger
/
Cell Line
/
Cell Movement
/
Neovascularization, Physiologic
/
Thrombospondin 1
/
Angiogenesis Inhibitors
/
RNA, Small Interfering
/
Endothelial Cells
/
Hydroxamic Acids
/
Neovascularization, Pathologic
Limits:
Animals
/
Humans
Language:
English
Journal:
Experimental & Molecular Medicine
Year:
2007
Type:
Article
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