Abstract 5580: Simvastatin induces expression of miRNA-200a and let-7c, leading to mRNA and protein expression of E-cadherin and reduced cell migration in PC-3 cells

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Simvastatin is a widely used cholesterol-lowering drug. Emerging evidence suggests that statins including simvastatin have other biological effects linked to a reduced risk of prostate cancer recurrence. We have examined the effect of simvastatin on invasive capacity of PC-3 cells, a cell line derived from a prostate cancer bone metastasis specimen. Our results showed that simvastatin treatment of PC3 cells at concentrations of 0.5 and 1 μM for 8 hours significantly increased the expression of miRNA-200a and let-7c. miRNA-200a and let-7c have been reported to be involved in epithelial to mesenchymal transition (EMT). At the same concentrations, simvastatin significantly induced the protein and mRNA expression of E-cadherin, a hallmark for EMT. In addition, simvastatin treatment of PC-3 cells caused markedly increased activities of Rho GTPases including RhoA, Cdc42 and Rac1. Collectively, these molecular events caused by simvastatin led to a significant reduction of PC-3 cell migration in a wound-healing experiment. Therefore, simvastatin exhibits a novel anti-migration activity against metastatic prostate cancer, suggesting a potential role for simvastatin in prevention of prostate cancer recurrence after prostatectomy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5580. doi:10.1158/1538-7445.AM2011-5580