PI3K Pathway Inhibition with NVP-BEZ235 Hinders Glycolytic Metabolism in Glioblastoma Multiforme Cells

Area of Science:

• Oncology
• Molecular Biology
• Cancer Metabolism

Background:

• Glioblastoma (GBM) is an aggressive brain cancer with limited treatment options.
• The PI3K/AKT/mTOR pathway is frequently activated in GBM, driving tumor growth and progression.

Purpose of the Study:

• To investigate the impact of PI3K/AKT/mTOR pathway inhibition on GBM cell metabolism.
• To identify key genes and pathways affected by dual PI3K and mTOR inhibition in GBM.

Main Methods:

• U87MG GBM cells were treated with NVP-BEZ235, a dual PI3K and mTOR inhibitor.
• RNA-sequencing (RNA-seq) was performed to identify differentially expressed genes.
• Gene Set Enrichment Analysis (GSEA) and bioinformatics analyses were used to assess pathway enrichment and clinical relevance.

Main Results:

• NVP-BEZ235 treatment significantly altered gene expression, with 7803 differentially regulated genes identified.
• Two glycolysis-related gene sets were significantly enriched in control samples compared to treated samples, indicating glycolytic inhibition.
• PI3K-impacted glycolytic genes were found to be over-expressed and co-expressed in GBM clinical samples, correlating with poor prognosis.

Conclusions:

• Dual PI3K/mTOR inhibition impacts GBM cell metabolism by suppressing glycolysis.
• Elevated expression of PI3K-regulated glycolytic genes is associated with poor patient outcomes in GBM.
• These findings offer novel insights into metabolic reprogramming in GBM and potential therapeutic strategies targeting the PI3K-mTOR pathway.