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

Abstract

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.

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Acknowledgements

This work was supported by research funds (No. 619) from National Institute of Genetic Engineering and Biotechnology, Tehran-Iran.

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Correspondence to Abdolkhaleg Deezagi.

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Deezagi, A., Safari, N. Rosuvastatin inhibit spheroid formation and epithelial–mesenchymal transition (EMT) in prostate cancer PC-3 cell line. Mol Biol Rep 47, 8727–8737 (2020). https://doi.org/10.1007/s11033-020-05918-1

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Keywords

  • Rosuvastatin
  • Prostate cancer
  • Epithelial–mesenchymal transition
  • Spheroid culture