EMB-driven glioblastoma multiforme progression via the MCT4/GPX3 axis: therapeutic inhibition by Ganxintriol A.

BACKGROUND: Embigin (EMB) is a transmembrane glycoprotein highly expressed in glioblastoma multiforme (GBM), yet its role in GBM progression remains unclear. In this study, we investigate the function of intracellular EMB in promoting GBM progression and evaluate the effect of Ganxintriol A, a traditional Chinese herbal extract, in GBM treatment.

METHODS: Bioinformatics datasets were utilized to assess EMB expression and its prognostic value in GBM patients. In vitro experiments such as PCR、western blot,CCK8,transwell,wound healing,clone formation and flow cytometry assays were conducted to examine EMB's biological functions and underlying mechanisms in GBM cell lines. Additionally, we constructed a subcutaneous tumor model in nude mice and evaluated the effect of traditional Chinese medicine extract Ganxintriol A on the progression of GBM through in vivo and in vitro experiments.

RESULTS: EMB is highly expressed in GBM and is associated with poor prognosis in GBM patients. EMB overexpression accelerated GBM progression, whereas EMB knockdown had the opposite effect. Further analysis revealed that EMB upregulated epithelial-mesenchymal transition (EMT) and glycolysis while maintaining glutathione (GSH) redox balance by inducing monocarboxylate transporter 4 (MCT4) and glutathione peroxidase 3 (GPX3) expression. Treatment with Ganxintriol A significantly downregulated EMB expression, effectively inhibiting GBM progression both in vitro and in vivo.

CONCLUSIONS: This study highlights EMB as an independent prognostic biomarker for GBM and reveals a novel mechanism by which EMB drives GBM progression. Additionally, Ganxintriol A is identified as a promising therapeutic candidate for GBM treatment.