Investigation into the synergistic effect of atorvastatin combined with ultrasound stimulation for anti-glioma therapy.

Glioblastoma (GBM) is an aggressive, malignant brain tumor marked by rapid growth and invasiveness. Ultrasound (US) stimulation has emerged as a potential therapeutic approach for the management of GBM. Atorvastatin (ATO), a drug widely used to treat hyperlipidemia, has also been recognized for its anticancer properties, including inhibition of cell proliferation, induction of cell cycle arrest and promotion of apoptosis. Despite these promising attributes, the combined effectiveness of ATO and US stimulation in GBM treatment remains unclear. The present study aimed to explore the potential synergistic effects of ATO and US stimulation on C6 glioma cells. The optimal concentration of ATO and calibrated US parameters were determined in the present study. The cells were treated with ATO or US, followed by assessments of cellular viability and reactive oxygen species (ROS) to establish the most effective ATO dose and US parameters. The cells were then treated with ATO, US or their combination, and cellular viability, ROS levels, ATP production, tumor cell migration and the impact on downstream molecular pathways, particularly the AKT/mTOR signaling pathway, which is key for cell survival and proliferation, were assessed. The present findings revealed that ATO independently suppressed glioma cell viability by elevating ROS levels and reducing ATP production, and it showed a trend toward impairing tumor cell migration. These effects were notably associated with downregulation of the AKT axis, which indicated disruption of key survival mechanisms within the tumor cells. However, the anticipated synergistic effect of combining ATO with US stimulation was not observed under the tested conditions, thus suggesting that US stimulation did not further augment the therapeutic effect of ATO. While the combination therapy did not yield additive benefits, ATO alone exhibited notable potential as a therapeutic agent against glioma. In conclusion, the present study highlighted the need for further research on the role of ATO to further harness its anticancer properties in the context of GBM treatment.