Ginsenoside Rg3 attenuates cell migration via inhibition of aquaporin 1 expression in PC-3M prostate cancer cells
- 作者：Xue-Yang Pan ; Hao Guo ; Jing Han ; Feng Hao ; Yu An ; Yan Xu ; Yilixiati Xiaokaiti ; Yan Pan ; Xue-Jun Li ; xjli@bjmu.edu.cn
- 关键词：Ginsenoside Rg3 ; Cell migration ; PC-3M cells ; Aquaporin 1 ; p38 MAPK ; Deletion analysis
- 刊名：European Journal of Pharmacology
- 出版年：2012
- 期刊代码：24_00142999
- 类别：neu
- 出版时间：15 May, 2012
- 卷：683
- 期：1-3
- 页码：27-34
- 文件大小：1026 K
摘要
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 渭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 鈭?#xA0;1000 bp to 鈭?#xA0;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.