Statins improve survival by inhibiting spontaneous metastasis and tumor growth in
a mouse melanoma model
#MMPMID26693069
Tsubaki M
; Takeda T
; Kino T
; Obata N
; Itoh T
; Imano M
; Mashimo K
; Fujiwara D
; Sakaguchi K
; Satou T
; Nishida S
Am J Cancer Res
2015[]; 5
(10
): 3186-97
PMID26693069
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Metastatic melanoma is a life-threatening disease for which no effective
treatment is currently available. In melanoma cells, Rho overexpression promotes
invasion and metastasis. However, the effect of statins on spontaneous metastasis
and tumor growth remains unclear. In the present study, we investigated the
mechanism of statin-mediated tumor growth and metastasis inhibition in an in vivo
model. We found that statins significantly inhibited spontaneous metastasis and
tumor growth. Statins inhibited the mRNA expression and enzymatic activities of
matrix metalloproteinases (MMPs) in vivo and also suppressed the mRNA and protein
expression of very late antigens (VLAs). Moreover, statins inhibited the
prenylation of Rho as well as the phosphorylation of LIM kinase, serum response
factor (SRF), and c-Fos downstream of the Rho signaling pathway. In addition,
statins enhanced p53, p21, and p27 expression and reduced phosphorylation of
cyclin-dependent kinase and expression of cyclin D1 and E2. These results
indicate that statins suppress Rho signaling pathways, thereby inhibiting tumor
metastasis and growth. Furthermore, statins markedly improved the survival rate
in a metastasis model, suggesting that statins have potential clinical
applications for the treatment of metastatic cancers.
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