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Sci Rep. 2016 Oct 25;6:35783. doi: 10.1038/srep35783.

Simvastatin induces cell cycle arrest and inhibits proliferation of bladder cancer cells via PPARγ signalling pathway.

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Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Department of Endocrinology, The First Affiliated Hospital of Zhejiang University, Hangzhou, China.
Marlene and Stewart Greenebaum Cancer Center, School of Medicine, University of Maryland, Baltimore, MD, USA.
Medical Research Institute, School of Medicine, Wuhan University, Wuhan, China.
College of Life Science, Wuhan University, Wuhan, China.
Center for Medical Science Research, Zhongnan Hospital of Wuhan University, Wuhan, China.


Simvastatin is currently one of the most common drugs for old patients with hyperlipidemia, hypercholesterolemia and atherosclerotic diseases by reducing cholesterol level and anti-lipid properties. Importantly, simvastatin has also been reported to have anti-tumor effect, but the underlying mechanism is largely unknown. We collected several human bladder samples and performed microarray. Data analysis suggested bladder cancer (BCa) was significantly associated with fatty acid/lipid metabolism via PPAR signalling pathway. We observed simvastatin did not trigger BCa cell apoptosis, but reduced cell proliferation in a dose- and time-dependent manner, accompanied by PPARγ-activation. Moreover, flow cytometry analysis indicated that simvastatin induced cell cycle arrest at G0/G1 phase, suggested by downregulation of CDK4/6 and Cyclin D1. Furthermore, simvastatin suppressed BCa cell metastasis by inhibiting EMT and affecting AKT/GSK3β. More importantly, we found that the cell cycle arrest at G0/G1 phase and the alterations of CDK4/6 and Cyclin D1 triggered by simvastatin could be recovered by PPARγ-antagonist (GW9662), whereas the treatment of PPARα-antagonist (GW6471) shown no significant effects on the BCa cells. Taken together, our study for the first time revealed that simvastatin inhibited bladder cancer cell proliferation and induced cell cycle arrest at G1/G0 phase via PPARγ signalling pathway.

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