Department of Molecular Medicine, National Institute of Genetic Engineering and Biotechnology, Km. 17, Karaj-Tehran freeway, Pajouhesh Blvd., P.O.Box 14155-6343, Tehran, Iran.
Mol Biol Rep. 2020 Nov;47(11):8727-8737. doi: 10.1007/s11033-020-05918-1. Epub 2020 Oct 21.
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 (R = 0.89). Vimentin and Zeb-1 expressions were decreased up to 40 and 20% of untreated control cells expression level respectively, (R = 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 (R = 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.
越来越多的证据表明他汀类药物具有抗肿瘤活性。在癌症的转移和侵袭中，癌细胞的上皮-间充质转化（EMT）是一个重要过程。我们的目标是了解罗苏伐他汀对贴壁二维（2D）和球体三维（3D）培养的人前列腺癌细胞系 PC-3 细胞 EMT 过程的影响。PC-3 细胞在贴壁和/或球体培养系统中培养。用不同浓度的罗苏伐他汀处理细胞。96 小时后，分析细胞增殖、活力、球体的类型和数量、E-钙粘蛋白、波形蛋白和 Zeb-1 的表达。结果表明，罗苏伐他汀抑制细胞增殖而无明显细胞毒性。罗苏伐他汀以剂量依赖的方式抑制球体形成和球体大小。在 2D 培养中，E-钙粘蛋白的表达呈剂量依赖性线性增加至 2.0 倍（R=0.89）。Vimentin 和 Zeb-1 的表达分别降低至未处理对照细胞表达水平的 40%和 20%（R=0.99 和 0.92）。在 3D 系统中，E-钙粘蛋白的表达没有明显变化，但与 2D 系统相比，Vimentin 和 Zeb-1 的表达分别降低至未处理对照细胞表达水平的 70%和 40%，呈剂量依赖性线性（R=0.36 和 0.90）。我们的发现表明，罗苏伐他汀抑制 PC-3 细胞的增殖和球体形成。这种抑制伴随着 EMT 标志物的抑制。因此，这种降胆固醇药物可能在预防和抑制雄激素依赖型前列腺癌中的癌症方面具有潜力。
