Graphene Oxide May Potentiate the Antitumor Efficacy of Bortezomib in Human Glioblastoma Multiforme Cells: An In Vitro Study

Glioblastoma multiforme (GBM) remains one of the most aggressive and treatment-resistant brain tumors, characterized by rapid proliferation and poor patient prognosis. Novel therapeutic strategies are urgently needed to improve clinical outcomes. In this study, we investigated the cytotoxic and pro-apoptotic effects of bortezomib (BORT), a proteasome inhibitor, and graphene oxide (GO), a nanomaterial with known anticancer potential, on human glioblastoma cell lines. Treatment with BORT and GO, both individually and in combination, significantly reduced cell viability in a dose-dependent manner, as determined by MTT. In this study we observed revealed enhanced apoptotic cell death, accompanied by increased activation of both caspase-8 and caspase-9, indicating simultaneous engagement of extrinsic and intrinsic apoptotic pathways. Western blot analysis demonstrated downregulation of anti-apoptotic proteins Bcl-2 and upregulation of pro-apoptotic markers (NOXA, cleaved PARP). A central finding of this work is the pronounced increase in intracellular reactive oxygen species (ROS) levels following BORT–GO treatment. The elevated ROS levels observed in BORT–GO–treated cells compared with free bortezomib therefore suggest a synergistic mechanism in which GO-mediated oxidative stress amplifies proteasome inhibition–induced apoptosis, which is particularly visible in the LN-229 line. Notably, the combination of BORT and GO exhibited synergistic effects, suggesting a potential cooperative mechanism through proteasome inhibition and oxidative stress induction. These findings indicate that graphene oxide may potentiate the antitumor efficacy of bortezomib and support further investigation of this combination as a promising therapeutic approach for glioblastoma.