Related Experiment Video
Updated: Dec 8, 2025
A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells
Published on: March 28, 2021
Sphingosine‑1‑phosphate analogue FTY720 exhibits a potent anti‑proliferative effect on glioblastoma cells
M A Kolodziej1, B Al Barim2, J Nagl1
1Department of Neurosurgery, Justus Liebig University Giessen, D‑35392 Giessen, Germany.
Abstract:
Sphingosine‑1‑phosphate (S1P) plays a key role in cell survival, growth, migration, and in angiogenesis. In glioma, it triggers the activity of the S1P‑receptor 1 and of the sphingosine kinase 1; thus influencing the survival rate of patients. The aim of the present study was to investigate the anti‑proliferative effect of the S1P analogue FTY720 (fingolimod) in glioblastoma (GBM) cells. A172, G28, and U87 cells were incubated with micromolar concentrations of FTY720 or temozolomide (TMZ) for 24 to 72 h. Proliferation and half maximal inhibitory concentration (IC50) were determined by using the xCELLigence system. FACS analysis was performed to check the cell cycle distribution of the cells after a 72‑h incubation with FTY720. This was then compared to TMZ‑incubated and to untreated cells. Gene expression was detected by RT‑qPCR in A172, G28, U87 and three primary GBM‑derived cell lines. FTY720 was able to reduce the number of viable cells. The IC50 value was 4.6 µM in A172 cells, 17.3 µM in G28 cells, and 25.2 µM in U87 cells. FTY720 caused a significant arrest of the cell cycle in all cells and stabilized or over‑expressed the level of AKT1, MAPK1, PKCE, RAC1, and ROCK1 transcripts. The TP53 transcript level remained stable or was downregulated after treatment with FTY720. FTY720 may be a promising target drug for the treatment of GBM, as it has a strong anti‑proliferative effect on GBM cells.
Insights
The sphingosine-1-phosphate (S1P) analogue FTY720 (fingolimod) demonstrated significant anti-proliferative effects in glioblastoma (GBM) cells. FTY720 reduced cell viability and arrested the cell cycle, indicating its potential as a GBM therapeutic.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Sphingosine-1-phosphate (S1P) signaling is implicated in cancer progression, particularly in glioma.
- S1P receptor 1 and sphingosine kinase 1 activity influence patient survival in glioma.
- Glioblastoma (GBM) remains a challenging malignancy with limited effective treatments.
Purpose of the Study:
- To investigate the anti-proliferative efficacy of the S1P analogue FTY720 (fingolimod) in glioblastoma (GBM) cells.
- To compare the effects of FTY720 with temozolomide (TMZ), a standard GBM treatment.
- To elucidate the molecular mechanisms underlying FTY720's action in GBM.
Main Methods:
- GBM cell lines (A172, G28, U87) and primary GBM cells were treated with FTY720 or TMZ.
- Cell proliferation and half maximal inhibitory concentration (IC50) were assessed using the xCELLigence system.
- Cell cycle distribution was analyzed by FACS, and gene expression was quantified by RT-qPCR.
Main Results:
- FTY720 significantly reduced the viability of GBM cells, with varying IC50 values across cell lines.
- FTY720 induced a notable cell cycle arrest in all tested GBM cells.
- FTY720 modulated the expression of key genes involved in cell survival and proliferation, including AKT1, MAPK1, PKCE, RAC1, and ROCK1, while TP53 levels remained stable or decreased.
Conclusions:
- FTY720 exhibits potent anti-proliferative activity against glioblastoma cells.
- FTY720's ability to arrest the cell cycle and modulate specific gene expression pathways suggests its therapeutic potential.
- FTY720 represents a promising candidate for novel glioblastoma treatment strategies.
More Related Videos
07:52Fluorescence Molecular Tomography for In Vivo Imaging of Glioblastoma Xenografts
Published on: April 26, 2018
10:28Flow Cytometry-based Drug Screening System for the Identification of Small Molecules That Promote Cellular Differentiation of Glioblastoma Stem Cells
Published on: January 10, 2018