Combined Applications of Repurposed Drugs and Their Detrimental Effects on Glioblastoma Cells.

BACKGROUND/AIM: Glioblastoma multiforme (GBM) is a malignant primary brain tumor with high rates of recurrence. This study aimed to investigate the effect of repurposed drug combinations on GBM.

MATERIALS AND

METHODS

Viability of U87 MG and 11ST patient-derived GMB cell lines, after valproic acid, tranylcypromine or riluzole alone, in different combinations, as well as combined with standard temozolomide chemotherapy was examined using the MTT assay. Proliferation, mRNA level of tissue factor pathway inhibitor 2 (TFPI2), and cell invasion were evaluated using anti-Ki-67 antibody staining, reverse transcriptase-polymerase chain reaction and xCELLigence system.

RESULTS

The strongest effect on cell viability was achieved by the combination of riluzole with valproic acid (U87MG: 27.2%, 11ST: 25.99%). Tranylcypromine significantly enhanced the effect of temozolomide when used in combination, as did valproic acid. The normally high proliferation of GBM significantly declined under treatment with valproic acid with tranylcypromine (p=0.01). Finally, we observed reduction of invasion comparing single tranylcypromine to its combination with valproic acid or riluzole.

CONCLUSION

These results support the idea that combinations of drugs could increase the treatment efficiency of GBM.