摘要
桔梗皂苷D(PD),一种源自桔梗的主要皂苷,对前列腺癌细胞株(PC3, DU145和 LNCaP 细胞)发挥毒性作用,IC50值从11.17到26.13μmol/L,而对RWPE-1细胞(一种非恶性人类前列腺上皮细胞株)无显著影响。这些细胞系的进一步研究表明PD可强有力地影响细胞增殖(由溴脱氧尿苷试验测定)、诱导细胞凋亡(由膜联蛋白V-FITC流式细胞术测定)和引起细胞周期抑制(由PI染色法测定)。用PD处理48小时,DU145和LNCaP细胞被抑制在G0 /G1期,PC3细胞被抑制在G2/M期。免疫印迹分析表明PD增加 FOXO3a转录因子的表达、降低 p-FOXO3a 和MDM2的表达、增加FOXO-应答基因、p21和p27的表达。MDM2沉默(由siRNA-MDM2暂时性的)增加PD诱导的FOXO3a蛋白表达,而MDM2过度表达(通过 pcDNA3-MDM2质粒在细胞内暂时转染) 降低PD诱导的FOXO3a蛋白表达。此外,PD的剂量依赖抑制BALB/c裸鼠中PC3移植瘤的生长。切除移植瘤的免疫印迹分析表明相似的蛋白表达的变化也发生在体内。这些结果表明PD在体外、体内抗前列腺癌显示了显著活性。FOXO3a转录因子似乎参与了PD的活动。所有的这些发现为这种药物治疗人类前列腺癌的未来发展提供了基础。
关键词: 细胞周期,FOXO3a,MDM2,桔梗皂苷 D,前列腺癌。
图形摘要
Current Cancer Drug Targets
Title:Platycodin D Induces Tumor Growth Arrest by Activating FOXO3a Expression in Prostate Cancer in vitro and in vivo
Volume: 14 Issue: 9
Author(s): Rui Zhou, Zongliang Lu, Kai Liu, Jing Guo, Jie Liu, Yong Zhou, Jian Yang, Mantian Mi and Hongxia Xu
Affiliation:
关键词: 细胞周期,FOXO3a,MDM2,桔梗皂苷 D,前列腺癌。
摘要: Platycodin D (PD), a major saponin derived from Platycodin grandiflorum, exerted cytotoxicity against prostate cancer cell lines (PC3, DU145 and LNCaP cells) with IC50 values in the range of 11.17 to 26.13μmol/L, whereas RWPE-1cells (a non-malignant human prostate epithelial cell line) were not significantly affected. A further study in these cell lines showed that PD could potently affect cell proliferation (indicated by the bromodeoxyuridine assay), induce cell apoptosis (determined by Annexin V-FITC flow cytometry) and cause cell cycle arrest (indicated by PI staining). After being treated with PD for 48 hours, DU145 and LNCaP cells were arrested in the G0 /G1 phase, and PC3 cells were arrested in the G2/M phase. A Western blotting analysis indicated that PD increased the expression of the FOXO3a transcription factor, decreased the expression of p-FOXO3a and MDM2 and increased the expression of FOXO-responsive genes, p21 and p27. MDM2 silencing (transiently by siRNA-MDM2) increased the PD-induced FOXO3a protein expression, while MDM2 overexpression (in cells transiently transfected with a pcDNA3-MDM2 plasmid) decreased the PD-induced expression of the FOXO3a protein. Moreover, PD dose-dependently inhibited the growth of PC3 xenograft tumors in BALB/c nude mice. A Western blotting analysis of the excised xenograft tumors indicated that similar changes in protein expression also occurred in vivo. These results suggest that PD exhibits significant activity against prostate cancer in vitro and in vivo. The FOXO3a transcription factor appears to be involved in the activity of PD. Together, all of these findings provide a basis for the future development of this agent for human prostate cancer therapy.
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Cite this article as:
Rui Zhou, Zongliang Lu, Kai Liu, Jing Guo, Jie Liu, Yong Zhou, Jian Yang, Mantian Mi and Hongxia Xu , Platycodin D Induces Tumor Growth Arrest by Activating FOXO3a Expression in Prostate Cancer in vitro and in vivo, Current Cancer Drug Targets 2014; 14 (9) . https://dx.doi.org/10.2174/1568009614666141128104642
DOI https://dx.doi.org/10.2174/1568009614666141128104642 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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