Euxanthone represses the proliferation, migration, and invasion of glioblastoma cells by modulating STAT3/SHP-1 signaling

Glioblastoma is one of the most prevalent primary malignant brain tumors. Glioblastoma often develops resistance to conventional chemoradiotherapy, and thus, new ways to treat glioblastoma are urgently required. The aim of this study was to investigate the effect of euxanthone on the anticancer activities of glioblastoma and its potential mechanism. The U87 and U251 glioblastoma cell lines were cultured in media containing different concentrations of euxanthone. CCK-8 and colony formation assay were used to evaluate the cell proliferation. Cell migration and invasion were evaluated by wound healing and Transwell assays. Flow cytometry was used to assess the cell cycle and apoptosis rate. TUNEL assay was also employed to evaluate the apoptosis rate. Gene and protein expressions were determined by RT-qPCR and western blotting, respectively. A xenograft model was established to evaluate the efficacy of euxanthone in vivo. Euxanthone significantly repressed cell viability, migration, invasion, and epithelial-to-mesenchymal transition of U87 and U251 cells; and increased the rate of apoptosis. Western blotting results revealed that the levels of p21, p27, cleaved caspase-3, Bax, TIMP-3, and E-cadherin were upregulated while, the levels of CDK4, CDK6, pro-caspase-3, Bcl-2, MMP-2, MMP-9, N-cadherin, and Vimentin were downregulated by euxanthone. In addition, the expression of p-STAT3 was decreased, while the expression of SHP-1 was upregulated by euxanthone. We proposed that euxanthone could repress the malignant behavior of glioblastoma cells through suppression of STAT3 phosphorylation and activation of SHP-1. Further, in vivo data demonstrated that euxanthone repressed tumor growth and promoted apoptosis.