The Combination of 5-FU and Resveratrol Can Suppress the Growth of Glioblastoma Cells Through Downregulation of TRPM2 and ß-Catenin.

ABSTRACT

Glioblastoma multiforme (GBM) is the most common as well as the most fatal primary malignant tumor of the central nervous system (CNS), which still lacks a definitive cure. 5-FU is an anti-metabolite anti-cancer agent which has shown promising results for GBM treatment. Resveratrol (Res) is a phytochemical anti-oxidant that has also been effective in suppressing the progression of GBM. The combination of 5-FU and Res has been studied in a variety of cancers, but no study has assessed this combination in GBM. In this study, we investigated how 5-FU and Res, in combination and alone, may affect the growth and apoptosis of GBM cells and also the potential of TRPM2 and ß-catenin as the mediator of their effects. U87 cells were cultured as the in vitro model. MTT assay was used for measuring cellular growth, and RT-qPCR was used to measure the level of caspase-3, TRPM2, and ß-catenin; caspase-3 level served as the indicator of apoptotic rate. 5-FU and Res, in combination and alone, suppressed the growth while promoting the apoptosis of U87 cells; these effects were significantly greater when they were used in combination. RT-qPCR showed downregulation of TRPM-2 and ß-catenin in response to this combination, which suggested that these two molecules may mediate the cited anti-oncogenic effects. In conclusion, our study confirmed the synergism between 5-FU and Res in suppressing the progression of GBM and suggested the putative axis of TRPM2/ ß-catenin as the downstream mediator of this therapeutic regime. Future studies may be able to approve the eligibility of this therapeutic regime for GBM treatment and also the underlying mechanism.