Artikel
Bcl-2/Bcl-xL inhibition enhances the anti-neoplastic activity of photodynamic therapy with 5-aminolevulinic acid against glioblastoma cells in vitro
Verstärkung der anti-neoplastischen Aktivität von photodynamischer Therapie mit 5-Aminolävulinsäure gegen Glioblastomzellen durch Hemmung von Bcl-2/Bcl-xL in vitro
Suche in Medline nach
Autoren
Veröffentlicht: | 26. Juni 2020 |
---|---|
Veröffentlicht mit Erratum: | 14. September 2020 |
Gliederung
Text
Objective: In this study, we examined whether inhibition of the anti-apoptotic Bcl-2 family proteins Bcl-2 and Bcl-xL enhances the biological effects of photodynamic therapy with 5-aminolevulinic acid in an in vitro setting of glioblastoma.
Methods: Pre-clinical testing of microcontroller-based devices emitting light of 405 or 635 nm wavelengths in combination with exposure to 5-aminolevulinic acid and the Bcl-2/Bcl-xL inhibitor ABT-263 was performed in human established, primary cultured glioblastoma cells and glioma stem-like cells. We applied cell count analyses to assess cellular proliferation, annexin V/PI and TMRE staining to examine apoptosis, and Western blotting and specific knockdown experiments using siRNA to examine molecular mechanisms of action.
Results: Bcl-2/Bcl-xL inhibition had enhanced anti-proliferative effects in various types of glioblastoma cells when combined with photodynamic therapy. The combination treatment induced caspase-dependent apoptosis. On the molecular level, Bcl-2/Bcl-xL inhibition led to an upregulation of Mcl-1 which, however, was counteracted by an increased expression of NOXA when combined with photodynamic therapy.
Conclusion: These data suggest that Bcl-2/Bcl-xL inhibition enhances the susceptibility of glioblastoma cells towards photodynamic therapy. This observation is at least in part due to a cytotoxic effect of the combination treatment and likely linked to a shift of the cellular phenotype pro apoptosis in response to an increased NOXA/Mcl-1 ratio.