SDF-1/CXCR4　signaling　axis　determines　the　proliferative　potential　and　site-specific　cancer　metastasis.　Recent　studies　suggest　involvement　of　the　axis　and　steroidal　hormone　in　ovarian　cancer　metastasis.　Here　we　hypothesize　that　mifepristone　(RU486),　a　well-known　progesterone-based　abortifacient,　might　interfere　this　axis　and　inhibit　ovarian　cancer　metastasis.　Mifepristone　at　concentrations　＜　IC50　inhibited　expression　of　CXCR4　on　cell　surface　of　ovarian　cancer　SKOV-3　and　IGROV-1,　and　reduced　expression　of　the　intracellular　CXCR4　protein　and　its　related　mRNA　activated　by　SDF-1.　SDF-1　significantly　stimulated　proliferation　of　SKOV-3　and　IGROV-1　cells　with　concomitant　increases　in　intracellular　phosphorylation　of　Akt　and　ERK.　SDF-1　activated　cell　chemotatic　migration　and　actin　polymerization,　and　up-regulated　expression　of　MMP-2,　MMP-9,　COX-2,　VEGF　without　influencing　the　adhesion　molecules　ICAM-1　and　integrins　β1,　a1,　a3,　a5,　and　a6.　The　abovementioned　effects　of　SDF-1　could　be　antagonized　by　mifepristone　concentrationdependently,　and　CXCR4　antagonist　AMD3100.　Mifepristone　suppressed　the　SDF-1-　induced　migration,　invasion　and　adhesion　of　the　cancer　cells　to　extracellular　matrixes.　Three-day　pretreatment　of　nude　mice　with　mifepristone　(5　and　20　mg/kg/day)　followed　by　a　single　intraperitoneal　IGROV-1　inoculation,　along　with　repeated　SDF-　1　and　mifepristone　administrations　in　turn　every　other　day　for　36　days　significantly　reduced　ascitic　fluid,　metastatic　foci,　tumor　weight　and　immunoreactivity　of　CXCR4　in　comparison　with　the　SDF-1-treated　control.　Our　results　suggest　that　mifepristone　inhibit　SDF-1/CXCR4　signaling　axis,　may　have　preventive　and　therapeutic　effects　on　ovarian　cancer　metastasis.　©　Zheng　et　al.