Background:　Metastasis　is　the　key　phase　of　cancer　progression　that　characterizes　a　more　advanced　stage　and　a　poorer　prognosis.　The　majority　of　cancer　fatalities　occur　as　a　consequence　of　metastasis.　Objective:　Mifepristone　(RU486),　a　chemical　abortifacient,　has　recently　been　used　in　clinical　trials　for　psychotic　depression　and　cancer　chemotherapy.　As　the　most　predominant　biological　active　metabolite　of　mifepristone,　metapristone　is　being　developed　as　a　novel　cancer　metastasis　chemopreventive　agent　by　us.　However,　there　is　no　information　available　to　address　the　effects　of　metapristone　on　non-small　cell　lung　cancer　(NSCLC).　The　aim　of　our　study　was　to　investigate　the　inhibitory　effect　of　metapristone　on　the　proliferation　and　metastasis　of　NSCLC　cells.　Method:　In　the　present　study,　we　evaluated　the　efficacy　of　metapristone　on　the　growth,　migration　and　invasion　in　different　kinds　of　NSCLC　cells　(A549,　H1975　and　H1299),　and　further　investigated　the　underlying　mechanism　of　metapristone　by　real　time　PCR　and　western　blot　assay.　Results:　Metapristone　could　significantly　inhibit　the　proliferation,　migration　and　invasion　of　NSCLC　cells　through　suppressing　RAS/RAF/MEK/MAPK　and　PI3K/AKT　signaling　pathways.　Moreover,　metapristone　could　effectively　inhibit　the　formation　of　NSCLC　cells＇　cytoskeleton　in　a　concentration-dependent　manner,　which　possibly　led　to　the　inhibition　of　NSCLC　cells＇　migration.　Conclusion:　Overall,　it　was　preliminarily　demonstrated　that　metapristone　could　be　developed　as　a　useful　agent　to　show　anti-metastasis　activity　for　NSCLC.　(C)　2017　Elsevier　Masson　SAS.　All　rights　reserved.