Related Experiment Video
Updated: Apr 13, 2026
Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma
Published on: October 27, 2014
Combination treatment of TRAIL, DFMO and radiation for malignant glioma cells
George A Alexiou1, Konstantinos I Tsamis, Evrysthenis Vartholomatos
1Neurosurgical Institute, Medical School, University of Ioannina, PO Box 103, Neohoropoulo, Ioannina, Greece, alexiougrg@yahoo.gr.
Abstract:
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has shown potent and cancer-selective killing activity and drawn considerable attention as a promising therapy for cancer. Another promising cancer therapy is difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, which is oraly administered and well tolerated. Nevertheless, many types of cancer, including gliomas, have exhibited resistance to TRAIL-induced apoptosis and similarly the potency of DFMO should be enhanced to optimize therapeutic efficacy. In this study we sought to determine whether DFMO, in combination with TRAIL and radiation, could result in an enhanced anti-glioma effect in vitro. We investigated the effect of DFMO, TRAIL and radiation in various combinations on a panel of glioblastoma cell lines (A172, T98G, D54, U251MG). Viability and proliferation of the cells were examined with trypan blue exclusion assay, crystal violet and xCELLigence system. Apoptosis (Annexin-PI), cell cycle and activation of caspase-8 were tested with flow cytometry. BAD protein levels were determined by Western blot analysis. DFMO induced BAD overexpression. Combination treatment with DFMO, TRAIL and radiation significantly reduced cell viability in all cell lines tested. Increased induction of cell death and cell cycle arrest was confirmed with flow cytometry in A172 and D54 cell lines, while enhanced activation of annexin and caspase-8 was revealed in U251MG and T98G cells. The treatment of glioblastoma cell lines with combination of DFMO, TRAIL and radiation showed an enhanced effect. This combination treatment may represent a novel strategy for targeting glioblastoma.
Insights
Combining difluoromethylornithine (DFMO) with TRAIL and radiation significantly enhances anti-glioma effects. This novel strategy overcomes glioblastoma resistance, showing reduced cell viability and increased apoptosis in preclinical models.
Area of Science:
- Oncology
- Cancer Biology
- Molecular Therapeutics
Background:
- Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) exhibits cancer-selective cytotoxicity but faces resistance in many cancers, including gliomas.
- Difluoromethylornithine (DFMO), an ornithine decarboxylase inhibitor, is an orally administered, well-tolerated cancer therapeutic, but its efficacy requires enhancement.
- Glioblastoma often exhibits resistance to single-agent therapies, necessitating combination strategies for improved therapeutic outcomes.
Purpose of the Study:
- To investigate the synergistic effect of combining DFMO, TRAIL, and radiation against glioblastoma cell lines in vitro.
- To determine if this combination therapy can overcome resistance mechanisms and enhance anti-glioma activity.
Main Methods:
- Utilized a panel of glioblastoma cell lines (A172, T98G, D54, U251MG) for in vitro testing.
- Assessed cell viability and proliferation using trypan blue exclusion, crystal violet staining, and the xCELLigence system.
- Analyzed apoptosis (Annexin-PI staining), cell cycle progression, caspase-8 activation, and BAD protein levels via flow cytometry and Western blot.
Main Results:
- Combined treatment with DFMO, TRAIL, and radiation significantly reduced glioblastoma cell viability across all tested cell lines.
- Enhanced induction of apoptosis and cell cycle arrest was observed in A172 and D54 cells.
- Increased activation of apoptosis markers, including annexin and caspase-8, was noted in U251MG and T98G cells.
- DFMO was found to induce BAD protein overexpression, potentially contributing to enhanced apoptosis.
Conclusions:
- The combination of DFMO, TRAIL, and radiation demonstrates a significant synergistic anti-glioma effect in vitro.
- This multi-modal approach shows promise in overcoming glioblastoma resistance to individual therapies.
- This combination strategy represents a novel therapeutic approach for targeting glioblastoma.
Related Concept Videos
02:56Treatment Resistant Cancers
02:56Treatment Resistent Cancers
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
01:27Tumor Immunotherapy