Deng Jun-Li, Zhang Rui, Zeng Ying, Zhu Yuan-Shan, Wang Guo
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, People's Republic of China.
Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, People's Republic of China.
Cancer Manag Res. 2019 Jul 31;11:7231-7242. doi: 10.2147/CMAR.S212643. eCollection 2019.
In recent years, statins have been frequently investigated in neoplasms. However, the potential roles of statins on prostate cancer cells and the underlying mechanisms have not been fully elucidated. In current study, we explored the effect and molecular mechanism of statins on cell proliferation and apoptosis in prostate cancer cells.
Prostate cancer cell were treated with gradient doses of simvastatin and fluvastatin for 24-72 h. Cell proliferation was analyzed by using MTS assay and colony formation. Cell apoptosis was measured by Hoechst staining, flow cytometry and caspase-3 activity. Western blotting was used to evaluate the proteins levels.
Both simvastatin and fluvastatin produced a dose- and time-dependent inhibition of cell viability and colony formation while a promotion of cell apoptosis as evident with increases in caspase-3 activity, cleaved-caspase-3, cleaved-caspase-8 and cleaved-PARP levels in PC3 cells. Similar statin effects were observed in DU145 prostate cancer cells. Furthermore, statins produced a time- and dose-dependent reduction of phosphorylated-AKT and phosphorylated-FOXO1 levels in PC3 cells, and pretreatment of cells with an AKT phosphorylation inhibitor, MK2206, potentiated statins' effect.
Statins decrease cell proliferation and induce cell apoptosis, probably mediated via a downregulation of AKT/FOXO1 phosphorylation in prostate cancer cells, which may have a potential benefit in prostate cancer prevention and therapy.
近年来，他汀类药物在肿瘤领域受到频繁研究。然而，他汀类药物对前列腺癌细胞的潜在作用及其潜在机制尚未完全阐明。在本研究中，我们探讨了他汀类药物对前列腺癌细胞增殖和凋亡的影响及其分子机制。
用梯度剂量的辛伐他汀和氟伐他汀处理前列腺癌细胞24至72小时。采用MTS法和集落形成实验分析细胞增殖情况。通过Hoechst染色、流式细胞术和caspase-3活性检测细胞凋亡。采用蛋白质印迹法评估蛋白水平。
辛伐他汀和氟伐他汀均对细胞活力和集落形成产生剂量和时间依赖性抑制，同时促进细胞凋亡，PC3细胞中caspase-3活性、裂解的caspase-3、裂解的caspase-8和裂解的PARP水平升高即证明了这一点。在DU145前列腺癌细胞中也观察到类似的他汀类药物作用。此外，他汀类药物使PC3细胞中磷酸化AKT和磷酸化FOXO1水平呈时间和剂量依赖性降低，用AKT磷酸化抑制剂MK2206预处理细胞可增强他汀类药物的作用。
他汀类药物可降低细胞增殖并诱导细胞凋亡，可能是通过下调前列腺癌细胞中AKT/FOXO1磷酸化介导的，这可能对前列腺癌的预防和治疗具有潜在益处。
