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Anat Rec (Hoboken) ; 302(8): 1399-1408, 2019 08.
Article in English | MEDLINE | ID: mdl-30334373

ABSTRACT

Osteosarcoma (OS) is one of the most common malignancies of bone. This study was aimed to explore the anti-metastatic effect of euxanthone on OS. Adhesion assay and Transwell assay were used to examine the effect of euxanthone on adhesion, migration and invasion of OS cells. COX-2-over-expressing plasmid was applied to transfect OS cells to assess whether COX-2 affects the anti-metastatic function of euxanthone. PDCD4 knockdown and miR-21 mimic were applied to assess whether euxanthone suppresses the transactivation of c-jun via modulating miR-21-PDCD4 signaling. The effect of euxanthone in vivo was also examined by lung metastasis assay. Euxanthone, a xanthone derivative extracted from Polygala caudata, has been found to exhibit anti-neoplastic activities. In present study, our results showed that euxanthone suppressed cell adhesion, migration, and invasion in OS cells. Our experimental data also showed that repression of COX-2 by euxanthone mediated its anti-metastatic activities. Moreover, our findings revealed that euxanthone modulated the COX-2 expression through the miR-21/PDCD4/c-jun signaling pathway. The anti-metastatic activities of euxanthone were also validated in a pulmonary metastasis model. Taken together, our results highlighted the potential of euxanthone to be used in the treatment of OS. Anat Rec, 302:1399-1408, 2019. © 2018 Wiley Periodicals, Inc.


Subject(s)
Bone Neoplasms/drug therapy , Cyclooxygenase 2/chemistry , Gene Expression Regulation, Neoplastic/drug effects , Lung Neoplasms/drug therapy , Osteosarcoma/drug therapy , Xanthones/pharmacology , Animals , Apoptosis , Apoptosis Regulatory Proteins/genetics , Apoptosis Regulatory Proteins/metabolism , Bone Neoplasms/metabolism , Bone Neoplasms/pathology , Cell Adhesion , Cell Movement , Cell Proliferation , Humans , JNK Mitogen-Activated Protein Kinases/genetics , JNK Mitogen-Activated Protein Kinases/metabolism , Lung Neoplasms/metabolism , Lung Neoplasms/secondary , Mice , Mice, Inbred BALB C , Mice, Nude , MicroRNAs/genetics , Neoplasm Invasiveness , Osteosarcoma/metabolism , Osteosarcoma/pathology , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Signal Transduction , Tumor Cells, Cultured , Xenograft Model Antitumor Assays
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