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Effects of photodynamic therapy on glioma spheroids
A J Terzis1, A Dietze, R Bjerkvig
1Department of Neurosurgery, Medical University of Lübeck, Germany.
Abstract:
The present study describes the sensitivity of glioma cells to a haematoporphyrin derivative (Photosan-3) under laser activation (argon-pumped dye laser). The effects of photodynamic therapy (PDT) on cell growth, directional migration and cell invasion were investigated on two human glioma cell lines (GaMg and U-251 Mg). The directional cell migration and spheroid growth was determined for both cell lines exposed to increasing laser energy output (15-35J/cm2) with concentrations of 5 and 7 micrograms/ml of Photosan-3. Both cell lines showed a dose-dependent migratory response to increasing laser irradiation, that was more prominent in the 7 micrograms/ml treatment group. This effect occurred during the first 4 days after drug exposure. Also, spheroids from both cell lines showed a drug and laser output energy dose-dependent inhibition of growth which became apparent after a lag period of 6 days. The lag period was characterized by a decreased growth rate as compared with the control group. During this period the outer cell layers of the spheroids fell apart. The remaining spheroid tissue was not able to migrate and to regrow when exposed to the highest laser energy outputs (30-35J/cm2, 5 and 7 micrograms/ml Photosan-3). These spheroids showed, however, the ability for invasion when confronted with normal brain cell aggregated in vivo. Light microscopic observations of co-cultures between tumour tissue and brain cell aggregates revealed a normal tumour morphology. This indicates that the remaining tumour cells were not dead and could be stimulated to invade the normal tissue when exposed to a normal brain microenvironment.
Insights
Photodynamic therapy (PDT) using Photosan-3 and laser activation effectively inhibited glioma cell migration and spheroid growth in a dose-dependent manner. However, surviving cells retained invasive potential in a normal brain microenvironment.
Area of Science:
- Oncology
- Biomedical Engineering
- Photochemistry
Background:
- Glioma, a primary brain tumor, presents significant therapeutic challenges.
- Photodynamic therapy (PDT) offers a targeted approach for cancer treatment.
- Haematoporphyrin derivatives are photosensitizers used in PDT.
Purpose of the Study:
- To investigate the efficacy of Photosan-3 mediated PDT on human glioma cell lines.
- To assess the impact of PDT on glioma cell migration, invasion, and spheroid growth.
- To determine the dose-dependent effects of Photosan-3 concentration and laser energy on glioma cells.
Main Methods:
- Two human glioma cell lines (GaMg and U-251 Mg) were treated with Photosan-3 at varying concentrations (5 and 7 µg/ml).
- Cells and spheroids were exposed to controlled laser irradiation (argon-pumped dye laser, 15-35 J/cm²).
- Cell migration, spheroid growth, and invasion assays (co-culture with normal brain cells) were performed.
Main Results:
- Both cell lines exhibited dose-dependent inhibition of migration and spheroid growth with increasing Photosan-3 and laser energy.
- A significant migratory response was observed at 7 µg/ml Photosan-3.
- A lag period of 6 days preceded growth inhibition, with outer spheroid layers disintegrating.
- Remaining tumor cells, even after high laser exposure, demonstrated invasive potential in co-cultures with normal brain cells.
Conclusions:
- PDT with Photosan-3 and laser activation demonstrates significant anti-migratory and anti-proliferative effects on glioma cells.
- Despite PDT-induced growth inhibition, surviving glioma cells retain the capacity for invasion.
- Further research is needed to address the residual invasive potential of glioma cells post-PDT.