Mebendazole Attenuates Cellular Invasion in a 3D Culture Model of Meningioma by Disrupting Rho-GTPase-Mediated Microtubule Function

Meningioma is the most common primary brain tumour. Invasion into the brain is a diagnostic feature of grade II meningiomas and is associated with recurrence and poor prognosis. Mebendazole is a microtubule inhibitor typically prescribed as an anthelmintic. However, it has the potential to be repurposed for cancer treatment. Here, we aimed to assess the ability of mebendazole to inhibit meningioma cell invasion.

Primary patient-derived meningioma cell lines were cultured as 3D spheroids and embedded in an extracellular matrix-like matrix as an in vitro model of invasion. Mebendazole-treated and untreated control spheroids were analysed by mass spectrometry-based proteomics.

Untreated control spheroids were capable of invasion (9/10 grade I, 10/12 grade II). When treated with mebendazole, invasion was prevented in 89% of samples (8/9 grade I, 9/10 grade II). Mass spectrometry-based proteomics revealed differences between the two grades and between male and female samples within each grade.

Overall, mebendazole reduced meningioma cell invasion via Rho GTPase signalling and altered cytoskeletal dynamics in both male and female patient-derived spheroids. Clearly, more research is needed; however, due to its high tolerability, known safety profile, low cost, and ability to attenuate meningioma cell invasiveness, mebendazole has the potential to be a good candidate for being repurposed for the treatment of meningioma.