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Updated: Oct 19, 2025
The Clinical Application of Tumor Treating Fields Therapy in Glioblastoma
Published on: April 16, 2019
Antiproliferative effect of GTS-21 in glioblastoma cells
Malgorzata A Kolodziej1, Hanna Gött1, Benjamin Kopischke1
1Department of Neurosurgery, Justus-Liebig University Giessen, D-35392 Giessen, Germany.
Abstract:
Glioblastoma multiforme (GBM) is the most common malignant brain tumour in adults. The poor prognosis and short median overall survival of patients with GBM is associated with resistance to therapy after surgical and adjuvant treatment. The expression of various acetylcholine receptors (AChR) in GBM has been widely reported. The present study aimed to investigate the expression of cholinergic system-related genes in primary GBM and to explore the antiproliferative effect of 3-(2,4-dimethoxybenzylidene) anabaseine (GTS-21) in GBM cell lines. Therefore, the expression of 28 genes associated with the cholinergic system was detected using a customized RT2 Profiler PCR Array in 44 GBM and 5 healthy control brain tissue samples. In addition, the activity of GTS-21, an alpha 7 subunit nicotinic AChR (α7 nAChR) agonist, and that of α-bungarotoxin (α-BTX), an α7 nAChR antagonist, was determined in primary and established GBM cells. Therefore, the A172, U87 and G28 cell lines and primary GBM cells were treated with GTS-21, ACh or nicotine. Cell viability was evaluated using MTT assay at 24, 48 and 72 h following cell treatment with the corresponding compounds. The results revealed that the expression of cholinergic system-related components was notably downregulated, except that of cholinergic receptor nicotinic alpha 7 subunit (CHRNA7), in primary GBM and U87 cells. However, the dominant-negative duplicate form of CHRNA7 was also downregulated. Furthermore, A172 and G28 cells exhibited a heterogeneous gene expression pattern. Additionally, GTS-21 inhibited the proliferation of GBM cells in a dose- and time-dependent manner. Interestingly, treatment with α-BTX restored the proliferation of U87 cells, but not that of A172 and G28 cells. Collectively, the findings of the present study suggested that GTS-21 may inhibit the proliferation of GBM cells and may therefore serve as a novel therapeutic approach to the treatment of GBM, which warrants further investigation.
Insights
Glioblastoma multiforme (GBM) cells show altered cholinergic system gene expression. The alpha 7 nicotinic acetylcholine receptor (α7 nAChR) agonist GTS-21 demonstrated antiproliferative effects on GBM cells, suggesting a potential new therapy.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Pharmacology
Background:
- Glioblastoma multiforme (GBM) is an aggressive brain tumor with poor patient prognosis.
- Therapeutic resistance contributes to poor outcomes in GBM patients.
- Aberrant expression of acetylcholine receptors (AChRs) is implicated in GBM.
Purpose of the Study:
- To investigate cholinergic system gene expression in primary GBM.
- To explore the antiproliferative effects of GTS-21, an α7 nAChR agonist, on GBM cell lines.
Main Methods:
- RT2 Profiler PCR Array used to analyze 28 cholinergic system genes in 44 GBM tissues and 5 controls.
- GBM cell lines (A172, U87, G28) and primary cells treated with GTS-21, acetylcholine, or nicotine.
- Cell viability assessed via MTT assay at 24, 48, and 72 hours.
Main Results:
- Cholinergic system gene expression was generally downregulated in GBM, with exceptions including CHRNA7.
- GTS-21 significantly inhibited GBM cell proliferation in a dose- and time-dependent manner.
- α-bungarotoxin (α-BTX), an α7 nAChR antagonist, partially restored proliferation in U87 cells.
Conclusions:
- GTS-21 exhibits antiproliferative activity against GBM cells.
- The cholinergic system, particularly α7 nAChR, plays a role in GBM proliferation.
- GTS-21 represents a potential novel therapeutic strategy for GBM requiring further investigation.
