title: Dryofragin inhibits the migration and invasion of human osteosarcoma U2OS cells by suppressing MMP-2/9 and elevating TIMP-1/2 through PI3K/AKT and p38 MAPK signaling pathways.
abstract: Dryofragin, a phloroglucinol derivative extracted from Dryopteris fragrans (L.) Schott, was found to inhibit proliferation and induce apoptosis of tumor cells. However, the mechanism involved in the suppression of cancer cell metastasis by dryofragin remains unclear. Our study investigated the mechanisms for the antitumor properties of dryofragin on the migration and invasion of human osteosarcoma U2OS cells. Dryofragin suppressed the migration and invasive ability of U2OS cells, and it decreased the expression of MMP-2 and MMP-9 and elevated the expression of TIMP-1 and TIMP-2. Western blotting assays indicated that dryofragin was effective in suppressing the phosphorylation of phosphatidylinositide-3 kinase (PI3K), Akt, and p38 MAPK. These results suggest that dryofragin inhibited U2OS cell migration and invasion by reducing the expression of MMP-2 and MMP-9 and elevating the expression of TIMP-1 and TIMP-2 through the PI3K/AKT and p38 MAPK signaling pathways. Above all, we conclude that dryofragin represents an anti-invasive agent and may potentially be applicable in osteosarcoma therapy.
authors.affiliation: aDepartment of Orthopaedics, Shanghai Jiaotong University Affiliated Sixth People's Hospital bDepartment of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Su
authors.forename: Daqian
authors.initials: D
authors.lastname: Wan
authors.forename: Wenqi
authors.initials: W
authors.lastname: Song
mesh_terms: D001859:Bone Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D032492:Dryopteris / Q000737:chemistry; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology*; D012516:Osteosarcoma / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D010936:Plant Extracts / Q000494:pharmacology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D010936:Plant Extracts; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D048051:p38 Mitogen-Activated Protein Kinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9