Artikel
TTFields empowers the anti-glioblastoma activity of CUSP9v3 in vitro
TTFields führt zu einer Verstärkung der Aktivität von CUSP9v3 gegen Glioblastomzellen in vitro
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Veröffentlicht: | 25. Mai 2022 |
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Gliederung
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Objective: Drug repurposing is a promising strategy to accelerate the clinical use of therapeutics with anti-neoplastic activity. In this study, we examined whether Tumor Treating Fields (TTFields) enhance the biological effects of the repurposed CUSP9v3 regimen in an in vitro setting of glioblastoma.
Methods: We performed MTT-assays to examine effects of the combination treatment on the viability of established, primary cultured and stem-like glioblastoma cells. Staining with annexin V/propidium iodide followed by flow cytometry was done to assess pro-apoptotic effects. Specific protein expression of members from the Bcl-2 family of proteins was determined by Western blot analyses.
Results: TTFields had at least additive anti-proliferative effects across established, primary cultured and stem-like glioblastoma cells when combined with CUSP9v3. In addition, flow cytometric analyses revealed that a simultaneous treatment with TTFields and CUSP9v3 significantly increased the fraction of annexin V-positive (apoptotic) glioblastoma cells. On the molecular level, the combination treatment led to a significant reduction of Bcl-2 levels.
Conclusion: These data suggest that TTFields enhance the susceptibility of glioblastoma cells towards CUSP9v3, potentially allowing significant dose reduction and decreased toxicity. TTFields are widely used for the treatment of glioblastoma patients and CUSP9v3 was recently shown to have a favorable safety profile in a phase Ib/IIa trial (NCT02770378) which facilitates transition of a combined approach to the clinical setting and warrants further investigation.