gms | German Medical Science

Objective: After surgery, adjuvant chemotherapy is necessary for many brain tumours. This is often associated with undesirable effects, e.g. toxicity for neuronal tissue. Vincristine is a common used chemotherapeutic agent. As part of the PCV regimen, it finds its application at oligodendrogliomas or in case of recurrence in glioblastomas. This alkaloid can cause various side effects such as polyneuropathy or optic atrophy. The aim of this work is to reduce undesirable side effects without reducing the therapeutic response of the malignant cells. Previous studies could demonstrate neuroprotective properties of nimodipine. For this purpose, experiments were conducted with this calcium channel blocker in combination with vincristine.

Methods: Cell lines of schwann cells, neuronal cells and tumour cells (oligodendroglioma, glioblastoma) were cultured and pre-treated with 10µM or 20µM nimodipine. Vincristine was added after 24 hours in a concentration of 1µM or 5µM. After 24h and 48h, cell death was measured by LDH assay. In addition, Western Blot was performed to investigate anti-apoptotic cell signaling pathways. Therefore levels and phosphorylation of Akt (proteinkinase B) and LMO4 (LIM Domaine Only 4) were measured.

Results: Pre-treatment of Schwann cells and neuronal cells with nimodipine led to a significant reduction in cell death, which was accompanied by an increased activation of Akt and higher LMO4 expression after vincristine treatment. In contrast, treatment with nimodipine resulted in a better response to chemotherapy in oligodendroglioma cells with significant increase in cell death. In glioblastoma cells, we observed a consistently high to slightly increased effect regarding cell death.

Conclusion: The combination of nimodipine and vincristine may be able to prevent adverse effects such as polyneuropathy while improving tumour response to chemotherapy. Further studies are needed to verify these effects, e.g. in animal models.