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　beta　1,　a1,　a3,　a5,　and　a6.　The　above-mentioned　effects　of　SDF-1　could　be　antagonized　by　mifepristone　concentration-dependently,　and　CXCR4　antagonist　AMD3100.　Mifepristone　suppressed　the　SDF-1induced　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　SDF1　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.