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Ginsenoside Rg3 (Rg3), one of the major effective ingredients in ginseng, has been shown to have various biological effects including anti-cancer activities.In this study, we detected the anti-migration effect of Rg3 on a high-metastatic prostate cancer cell line, PC-3M, and observed its correlation with AQP1 water channel protein.Using wound healing assay and transwell migration assay, the results showed an inhibitory effects on PC-3M cell migration with the concentration of 1-10 pμmol·L-1 of Rg3.Simultaneously, the AQP1 expression was suppressed by Rg3 on both protein and mRNA level.Then the AQP1 was overexpressed by pcDNA3-AQP1 plasmid in PC-3M cells, we found that overexpression of AQP1 recovered the cell migration of PC-3M cells, which antagonized Rg3s inhibitory effect.On the other hand, after silencing the AQP1 expression by tranfected shRNA of AQP1 to PC-3M, the cell migration was decreased, similar to the effect of Rg3 treatment.The cell migration was inhibited lower than basehne level.In order to elucidate the regulatory mechanism, we tested the MAPK signaling pathway in PC-3M.Activation of p38 MAPK was observed after Rg3 treatment.To further explore the possible mechanism of Rg3 on AQP1 gene expression, we carried out the deletion analysis on the promoter region of AQP1 gene.Different length of promoter segments were inserted into luciferase vector and the dual-luciferase assay was used to assess which fragment was crucial for Rg3s effect on AQP1.The result from this assay suggested that the-1000 to-500 region of the promoter might be responsible for Rg3s effect.Further study will be designed basing on these data.The study uncovers the anti-migration effect of Rg3 in PC-3M cells and the role of AQP1 in the regulation process.