Alim Emre Basaran (Leipzig), Johannes Wach (Leipzig), Christoph Bach (Leipzig), Tia Detzer (Leipzig), Erdem Güresir (Leipzig), Frank Gaunitz (Leipzig)
The management and limited therapeutic options for high-grade meningiomas present a therapeutic challenge. Proteasome inhibitors have shown antiproliferative activity in glioblastoma in vivo and in vitro. Hence, there is a need to investigate the antiproliferative effect of proteasome inhibition in meningiomas.
Here, we investigated the antiproliferative effect of marizomib in all three WHO grades of meningiomas in vitro. We investigated two WHO grade 1, two WHO grade 2, and three WHO grade 3 primary meningiomas. WHO grading was performed according to the WHO classification system 2021. These studies with human primary meningioma cell cultures were performed with apoptosis and viability assays under 24-hour incubation.
Our results showed that the median effective dose (ED50) values for growth inhibition were at concentrations between 0.05 – 0.07 μM in WHO grade 1, 0.08-0.11 μM in WHO grade 2 and 0.1-0.3 μM in WHO grade 3 meningiomas. The Spearman correlation test showed a strong positive correlation between dose and anti-proliferative activity in each culture of all three WHO grades (R²=1.0).
We have shown that the blood-brain barrier penetrating proteasome inhibitor marizomib might be a promising therapeutic option for meningiomas.
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