Diosgenin, a steroidal saponin, inhibits migration and invasion of human prostate cancer PC-3 cells by reducing matrix metalloproteinases expression.
Diosgenin, a steroidal saponin, inhibits migration and invasion of human prostate cancer PC-3 cells by reducing matrix metalloproteinases expression.
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DOI：
10.1371/journal.pone.0020164
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Cheng HW
中科院分区：
文献类型：
--
作者：
Chen PS;Shih YW;Huang HC;Cheng HW
薯蓣皂苷元是一种从葫芦巴（Trigonella foenum graecum）中提取的甾体皂苷，在多种肿瘤细胞中具有抑制增殖和诱导凋亡等抗癌特性。然而，薯蓣皂苷元对肿瘤转移的影响尚不清楚。本研究旨在探讨薯蓣皂苷元对人前列腺癌PC-3细胞迁移和侵袭的影响。薯蓣皂苷元抑制PC-3细胞增殖呈剂量依赖性。无毒性剂量的薯蓣皂苷元分别通过体外伤口愈合实验和Boyden室侵袭实验抑制了细胞的迁移和侵袭。明胶酶谱分析表明，薯蓣皂苷元降低了基质金属蛋白酶-2 （MMP-2）和MMP-9的活性。黄芪皂苷元还能抑制基质金属蛋白酶-2、-9、-7和细胞外诱导剂EMMPRIN mRNA的表达，提高基质金属蛋白酶-2组织抑制剂TIMP-2的表达水平。此外，薯蓣皂苷元还能抑制PC-3细胞中血管内皮生长因子（VEGF）的表达和内皮细胞的管状形成。我们的免疫印迹实验表明，薯蓣皂苷元能有效抑制磷脂酰亚胺苷-3激酶（PI3K）、Akt、细胞外信号调节激酶（ERK）和c-Jun n -末端激酶（JNK）的磷酸化。此外，薯蓣皂苷元显著降低核因子κB （NF-κB）的核水平，表明薯蓣皂苷元抑制了NF-κB的活性。结果表明薯蓣皂苷元通过降低MMPs的表达抑制PC-3细胞的迁移和侵袭。它还能抑制ERK、JNK和PI3K/Akt信号通路以及NF-κB活性。这些发现揭示了薯蓣皂苷元在抗转移治疗中的新的治疗潜力。
Diosgenin, a steroidal saponin obtained from fenugreek (Trigonella foenum graecum), was found to exert anti-carcinogenic properties, such as inhibiting proliferation and inducing apoptosis in a variety of tumor cells. However, the effect of diosgenin on cancer metastasis remains unclear. The aim of the study is to examine the effect of diosgenin on migration and invasion in human prostate cancer PC-3 cells. Diosgenin inhibited proliferation of PC-3 cells in a dose-dependent manner. When treated with non-toxic doses of diosgenin, cell migration and invasion were markedly suppressed by in vitro wound healing assay and Boyden chamber invasion assay, respectively. Furthermore, diosgenin reduced the activities of matrix metalloproteinase-2 (MMP-2) and MMP-9 by gelatin zymography assay. The mRNA level of MMP-2, -9, -7 and extracellular inducer of matrix metalloproteinase (EMMPRIN) were also suppressed while tissue inhibitor of metalloproteinase-2 (TIMP-2) was increased by diosgenin. In addition, diosgenin abolished the expression of vascular endothelial growth factor (VEGF) in PC-3 cells and tube formation of endothelial cells. Our immunoblotting assays indicated that diosgenin potently suppressed the phosphorylation of phosphatidylinositide-3 kinase (PI3K), Akt, extracellular signal regulating kinase (ERK) and c-Jun N-terminal kinase (JNK). In addition, diosgenin significantly decreased the nuclear level of nuclear factor kappa B (NF-κB), suggesting that diosgenin inhibited NF-κB activity. The results suggested that diosgenin inhibited migration and invasion of PC-3 cells by reducing MMPs expression. It also inhibited ERK, JNK and PI3K/Akt signaling pathways as well as NF-κB activity. These findings reveal new therapeutic potential for diosgenin in anti-metastatic therapy.