Ginger extract inhibits c-MET activation and suppresses osteosarcoma in vitro and in vivo.

BACKGROUND: Osteosarcoma (OS) as an invasive and lethal malignancy showing a low 5-year survival rate requires novel therapeutic targets and their suppressors to improve prevention and treatment strategies. METHODS: Our research served to clarify the therapeutic potential of ginger extract and its underlying antineoplastic mechanisms in OS. In vitro studies were used to detect the anti-proliferation ability of ginger extract towards OS cells. Patient-derived xenograft (PDX) was performed to confirm whether ginger extract suppressed tumor growth. Cancer Heat Shock Protein (HSP) database was utilized to identify the potential target of ginger extract, which was subsequently validated through a computational docking model screening method, molecular dynamics simulations and pull-down assay. Analysis of the Gene Expression Omnibus (GEO) database revealed the c-MET expression among OS samples as well as the potential mechanism. Immunohistochemistry (IHC) staining corroborated the c-MET expression level among OS tissues relative to the controls. Functional studies involving c-MET knockdown among OS cell lines were produced to elucidate the functional role of c-MET in OS cellular processes. RESULTS: In vitro studies demonstrated that ginger extract administration impeded OS cell progress while inducing apoptosis and inhibiting migration. Moreover, in vivo tests unveiled that ginger extract prominently inhibited patient-derived xenograft (PDX) tumor development. Cancer HSP database analysis recognized c-MET as an underlying target of ginger extract, which was subsequently validated through a computational docking model screening, molecular dynamics simulations and pull-down assay. Analysis of the Gene Expression Omnibus (GEO) database combined with immunohistochemistry (IHC) staining corroborated the c-MET overexpression among OS tissues in contrast with the controls. Next, our study confirmed the significant suppression of cell progress and anchorage-independent growth, while concomitantly inducing apoptosis after c-MET knockdown, underscoring its prospect for a therapeutic target. CONCLUSION: Collectively, our findings show that c-MET is a prospective therapeutic target for OS. Ginger extract, a natural c-MET inhibitor, exhibits potent antineoplastic effects by suppressing OS growth both in vitro and in vivo, highlighting its prospect for a new therapeutic agent of this aggressive malignancy.