Efficient cell death induction in human glioblastoma cells by photodynamic treatment with Tetrahydroporphyrin-Tetratosylat (THPTS) and ionizing irradiation
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Peter Hambsch1, Yury P. Istomin3, Dimitri A. Tzerkovsky3, Ina Patties1, Jochen Neuhaus4, Rolf-Dieter Kortmann1, Stanislav Schastak2 and Annegret Glasow1
1Department of Radiation Therapy, University of Leipzig, 04103 Leipzig, Germany
2Department of Ophthalmology, University of Leipzig, 04103 Leipzig, Germany
3N. N. Alexandrov Republican Scientific and Practical Center of Oncology and Medical Radiology, 223040 Lesnoy, Republic of Belarus
4Department of Urology, University of Leipzig, 04103 Leipzig, Germany
Annegret Glasow, email: Annegret.Glasow@medizin.uni-leipzig.de
Keywords: photodynamic therapy, glioblastoma, THPTS, combination, ionizing radiation
Received: January 10, 2017 Accepted: August 04, 2017 Published: August 23, 2017
Background: 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.
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