Ginsenoside Rg3 attenuates cell migration via inhibition of aquaporin 1 expression in PC-3M prostate cancer cells
Ginsenoside Rg3 attenuates cell migration via inhibition of aquaporin 1 expression in PC-3M prostate cancer cells
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人参皂苷 Rg3 通过抑制 PC-3M 前列腺癌细胞中水通道蛋白 1 的表达来减弱细胞迁移
DOI：
10.1016/j.ejphar.2012.02.040
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发表时间：
2012-05-15
影响因子：
5
通讯作者：
Li, Xue-Jun
中科院分区：
文献类型：
--
作者：
Pan, Xue-Yang;Guo, Hao;Li, Xue-Jun
人参皂苷Rg3(Rg3)是人参根中发现的一种生物活性提取物，据报道在多种肿瘤模型中具有抗癌活性。Rg3对前列腺癌细胞的抗增殖作用已有很好的报道。为了测试RG3对前列腺癌是否有抗转移作用，我们用RG3处理高转移的PC-3M前列腺癌细胞系。我们发现Rg3(10 MU M)对PC-3M细胞的迁移有明显的抑制作用。同时，暴露于Rg3可抑制水通道蛋白1(AQP1)的表达，该蛋白此前已被报道参与细胞迁移。AQP1的过表达减弱了Rg3对细胞迁移的抑制，靶向AQP1的shRNA的引入消除了Rg3的抑制作用，尽管RNA干扰降低了细胞迁移的基础水平。在机制研究中，雌激素受体和糖皮质激素受体依赖的途径被证明不参与RG3对AQP1的调节。然而，Rg3处理触发了p38MAPK的激活，而p38MAPK的特异性抑制剂SB202190拮抗了Rg3诱导的AQP1和细胞迁移的调节，表明p38在调控过程中发挥了关键作用。用双荧光素酶分析方法对AQP1启动子区域进行了缺失分析，结果表明-1000~-200bp的启动子区域参与了RG3对AQP1的调控。总之，我们认为Rg3通过p38MAPK通路和作用于AQP1启动子的一些转录因子下调AQP1的表达，从而有效地抑制PC-3M细胞的迁移。(C)2012爱思唯尔B.V.保留所有权利。
Ginsenoside Rg3 (Rg3), one of the bioactive extracts found in ginseng root, was reported to have anti-cancer activity in various cancer models. The anti-proliferation effect of Rg3 on prostate cancer cells has been well reported. To test whether Rg3 has an anti-metastatic effect on prostate cancer, we treated a highly metastatic PC-3M prostate cancer cell line with Rg3. We found that Rg3 (10 mu M) led to remarkable inhibition of PC-3M cell migration. Simultaneously, exposure to Rg3 suppressed expression of the aquaporin 1 (AQP1) water channel protein, which has previously been reported to be involved in cell migration. Overexpression of AQP1 attenuated Rg3-induced inhibition of cell migration, and introduction of a shRNA targeting AQP1 abrogated the inhibitory effect of Rg3, although the basal level of cell migration was decreased by RNA interference. In mechanism study, estrogen receptor-and glucocorticoid receptor-dependent pathways are proved uninvolved in the AQP1 regulation by Rg3. However, Rg3 treatment triggered the activation of p38 MAPK; and SB202190, a specific inhibitor of p38 MAPK, antagonized the Rg3-induced regulation of AQP1 and cell migration, suggesting a crucial role for p38 in the regulation process. Deletion analysis of the promoter region of AQP1 was also conducted using dual-luciferase assay, which indicated that the -1000 bp to -200 bp promoter region was involved in the AQP1 regulation by Rg3. In all, we conclude that Rg3 effectively suppresses migration of PC-3M cells by down-regulating AQP1 expression through p38 MAPK pathway and some transcription factors acting on the AQP1 promoter. (C) 2012 Elsevier B.V. All rights reserved.