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Simvastatin blocks TGF-?1-induced epithelial-mesenchymal transition in human
prostate cancer cells
#MMPMID27123120
Xie F
; Liu J
; Li C
; Zhao Y
Oncol Lett
2016[May]; 11
(5
): 3377-3383
PMID27123120
show ga
In recent years, the use of statins has been reported to be associated with a
reduced risk of prostate cancer (PCa), particularly metastatic PCa. The
mechanisms underlying these epidemiological observations are poorly understood.
Epithelial-mesenchymal transition (EMT) is a critical initial step and a hallmark
for cancer metastasis. In the present study, the relationship between simvastatin
and EMT in PCa and the mechanism involved was investigated. It was demonstrated
that simvastatin inhibited the EMT as assessed by reduced expression of
N-cadherin and vimentin, and increased E-cadherin in TGF-?1 treated DU145 PCa
cells. Furthermore, simvastatin inhibited TGF-?1-induced migration and invasion
of DU145 cells. The TGF-?1/Smad pathway and non-Smad pathway were investigated in
simvastatin-treated DU145 cells. Simvastatin had no effect on TGF-?1-induced
phosphorylation of Smad2 and Smad3. In the non-Smad pathway, simvastatin reduced
TGF-?1-induced p38 MAPK phosphorylation, but had no effect on TGF-?1-induced
Erk1/2 phosphorylation. Simvastatin attenuated TGF-?1-induced EMT, cell migration
and invasion in DU145 cells. These effects may have been mediated by the
inhibition of p38 MAPK phosphorylation, not through the canonical Smad pathway.
Therefore simvastatin may be a promising therapeutic agent for treating PCa.
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