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Am J Pathol. 2009 Mar;174(3):1017-26. doi: 10.2353/ajpath.2009.080551. Epub 2009 Jan 29.

Ezetimibe is an inhibitor of tumor angiogenesis.

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  • 1Dept. of Orthopaedic Surgery, Harvard Medical School, Boston, MA 02115, USA. keith.solomon@childrens.harvard.edu

Abstract

Epidemiological and preclinical observations have suggested a role for one or more products of the mevalonate/cholesterol biosynthesis pathway in the progression of prostate cancer. In this study, we used ezetimibe (Zetia), a specific, FDA-approved, cholesterol uptake-blocking drug, in combination with either a hyper- or hypocholesterolemic diet, to show that elevated circulating cholesterol levels promote, whereas a reduction in circulating cholesterol levels retard, the growth of human prostate cancer xenograft tumors in mice. Circulating cholesterol levels also modified tumor angiogenesis; higher cholesterol levels increased microvessel density and other indicators of vascularity. Consistent with these data, the reduction of cholesterol levels also increased the levels of the angiogenesis inhibitor thrombospondin-1 in the xenografts. Our results thus suggest that hypercholesterolemia directly accelerates the growth of prostate carcinomas, and that the pharmacological reduction of serum cholesterol levels may retard prostate cancer growth by inhibiting tumor angiogenesis.

PMID:
19179610
PMCID:
PMC2665761
DOI:
10.2353/ajpath.2009.080551
[PubMed - indexed for MEDLINE]
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