Vor- und Nachteile der Kombinationsbehandlung von GBM-Zellen mit Riluzol und Metformin

Controlling glucose levels is one of the strategies to influence its deleterious effect on glioblastoma (GBM) progression. Metformin (Met) is a drug widely used in diabetic patients and its cytotoxic activity in GBM is due to a reduction in glucose levels. Riluzole (Ril) is an approved drug for the treatment of amyotrophic lateral sclerosis with a broad spectrum of action including anti-glutamatergic pharmacological properties as well as its involvement in glucose metabolism in GBM. Here we investigated the combined effect on GBM cells.

U87MG cells were treated with Ril (25 µM) and/or Met (1 mM). The expression of the following genes was analysed by quantitative PCR: TFPi2, N-cadherin. Migration was assessed using the xCELLigence system. Prior to the experiment, cells were pre-treated with either 25µM Ril or vehicle for 72 h. Migration rate was expressed as cell index after 5 h co-treatment.

The U87MG cells treated with Met showed a significant decrease in the expression of both TFPi2 and N-cadherin (***p), whereas riluzole significantly increased the expression of TFPi2 (***p) and decreased the expression of N-cadherin (**p). In the co-treatment group, the expression of the TFPi gene was significantly decreased compared to riluzole alone, but significantly increased compared to the control group. In addition, a significant increase in migration was observed in Met treated cells (**p), and co-treatment with riluzole further enhanced this effect.

A positive effect of co-treatment was observed in the case of TFPi2 expression levels compared to control or metformin alone. As the expression levels of N-cadherin in gliomas increase with pathological glioma grade, a positive effect - significant reduction - was observed with each treatment. A negative effect of the co-treatment was seen in the migration of this cells. Although this study is preliminary and requires further work, it offers another possibility for potential combinatorial treatment of GBM.