So far, glioblastomas cannot be cured by standard therapy and
have an extremely poor median survival of about 15 months. The photodynamic
therapy (PDT) with next generation photosensitizers, reaching a higher therapeutic
depth, might offer a new, adjuvant treatment strategy in brain cancer therapy. Here,
we investigated the effect of THPTS-PDT combined with ionizing irradiation (IR) on
glioblastoma cells in vitro and in vivo.
Results: THPTS colocalized to mitochondria and was not found in the nucleus.
THPTS (2–20 μg/ml)-PDT significantly reduced the proliferation, metabolic activity
and clonogenic survival and induced cell death mainly through apoptosis and
autophagy. THPTS-PDT combined with IR decreased the clonogenicity significantly
compared to single treatments. THPTS (≤ 300 μg/ml) alone showed no dark toxicity.
The maximum therapeutic depth of THPTS-PDT in C6 glioblastomas was 13 mm.
Materials and Methods: Three human glioblastoma cell lines (U-87 MG, A-172,
DBTRG-05MG) were incubated with THPTS (1–300 μg/ml) 3–24 hours before laser
treatment (760 nm, 30 J/cm²). THPTS localization and effects on metabolic activity,
proliferation, cell death mechanisms and long-term reproductive survival were
assessed. IR was conducted on an X-ray unit (0.813 Gy/min). Results were verified
in vivo on a subcutaneous C6 glioblastoma model in Wistar rats.
Conclusions: This study demonstrated efficient THPTS-PDT in glioblastoma cells,
in vitro and in vivo. The combinatorial effects of THPTS-PDT and IR are of specific
clinical interest as enhanced eradication of infiltrating glioblastoma cells in the tumor surrounding tissue might possibly reduce the commonly occurring local relapses.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:35442 |
| Date | 20 September 2019 |
| Creators | Hambsch, Peter Kurt |
| Contributors | Kortmann, Rolf-Dieter, Glasow, Annegret, Patties, Ina, Schastak, Stanislaw, Universität Leipzig |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | German, English |
| Detected Language | English |
| Type | info:eu-repo/semantics/acceptedVersion, doc-type:doctoralThesis, info:eu-repo/semantics/doctoralThesis, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
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