Simvastatin blocks TGF-β1-induced epithelial-mesenchymal transition in human prostate cancer cells.
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-β1 treated DU145 PCa cells. Furthermore, simvastatin inhibited TGF-β1-induced migration and invasion of DU145 cells. The TGF-β1/Smad pathway and non-Smad pathway were investigated in simvastatin-treated DU145 cells. Simvastatin had no effect on TGF-β1-induced phosphorylation of Smad2 and Smad3. In the non-Smad pathway, simvastatin reduced TGF-β1-induced p38 MAPK phosphorylation, but had no effect on TGF-β1-induced Erk1/2 phosphorylation. Simvastatin attenuated TGF-β1-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.
Department of Urology, Affiliated Hospital of Logistics University of Chinese People's Armed Police Forces, Tianjin 300162, P.R. China.
Feng
F
Xie
Department of Urology, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China.
Jie
J
Liu
Department of Urology, Affiliated Hospital of Logistics University of Chinese People's Armed Police Forces, Tianjin 300162, P.R. China.
Chengwen
C
Li
Department of Urology, Affiliated Hospital of Logistics University of Chinese People's Armed Police Forces, Tianjin 300162, P.R. China.
Yaorui
Y
Zhao
epithelial-mesenchymal transition; p38 mitogen-activated protein kinases; prostate cancer; simvastatin; transforming growth factor-β1