Rosuvastatin inhibit spheroid formation and epithelial-mesenchymal transition (EMT) in prostate cancer PC-3 cell line

There is a growing body of evidence suggesting antitumor activity of statins. In metastasis and invasion of cancer the Epithelial-Mesenchymal Transition (EMT) of cancerous cells is an important process. Our goal was to understand the effect of Rosuvastatin on the EMT process in human prostate cancer cell line PC-3 cells in adherent 2 dimensional (2D) and spheroid 3 dimensional (3D) culture. PC-3 cells were cultured in adherence and/or spheroid culture system. The cells were treated with different concentrations of Rosuvastatin. After 96 h, the cell proliferation, viability, type and number of spheroids, the expression of E-Cadherin, Vimentin and Zeb-1 were analyzed. The results show that Rosuvastatin inhibit cell proliferation without significant cytotoxicity. The spheroid formation and spheroid sizes were inhibited by Rousavastatin in a dose dependent manner. In 2D culture, expression of the E-Cadherin was increased up to 2.0 fold in a dose dependent linear manner (R² = 0.89). Vimentin and Zeb-1 expressions were decreased up to 40 and 20% of untreated control cells expression level respectively, (R² = 0.99 and 0.92). In 3D system, the expression of E-Cadherin did not show a significant change, but Vimentin and Zeb-1 expressions were decreased up to 70 and 40% of untreated control cells expression level respectively in a dose dependent linear manner in comparison to 2D system (R² = 0.36 and 0.90). Our finding indicates that Rousavastatin inhibit cell proliferation and spheroid formation of PC-3 cells. This inhibition accompanies by inhibition of EMT markers. Therefor, this cholesterol lowering agent could probably have potential in the prevention and suppression of cancer in androgen dependent prostate cancer.