The invasive nature of
malignant gliomas makes treatment by surgery alone extremely difficult. However, the preferential accumulation of photosensitisers in neoplastic tissues suggests
photodynamic therapy (
PDT) may be useful as an adjuvant
therapy following tumour resection. In this study, the potential use of three different photosensitisers, namely
Photofrin, 5-aminolevulinic
acid (5-ALA) and
calphostin C in the treatment of
glioma was investigated. The uptake, cytotoxicity on U87 and GBM6840
glioma cell lines were determined by flow cytometry and MTT assay respectively. Their effect on
glioma cell invasiveness was evaluated by (1) measuring the levels of matrix degradation
enzymes matrix metalloproteinase (MMP)-2 and -9 using
gelatin zymography, and (2)
Matrigel invasion assay. The results showed that uptake of
calphostin C reached saturation within 2 h, while
Photofrin and 5-ALA induced
protoporphyrin IX (
PpIX) levels elevated steadily up to 24 h. Photocytotoxic effect on the two
glioma cell lines was similar with LD50 at optimal uptake: 1 microg/mL
Photofrin at 1.5 J/cm(2); 1 mM 5-ALA at 2 J/cm(2) and 100 nM
calphostin C at 2 J/cm(2). The inhibition in cell proliferation after
Photofrin treatment was similar for both cell lines, which correlated to more cells being arrested in the G0/G1 phase of the cell cycle (P<0.01). By contrast, U87 was more sensitive to
calphostin C whereas GBM6840 was more susceptible to 5-ALA treatment. The ability of both cell lines to migrate through the
Matrigel artificial basement membrane was significantly reduced after
PDT (P<0.001). This might be due to a decreased production in MMP-2 and MMP-9, together with the reduction of adhesion molecule expression.
Photofrin was most superior in inhibiting cell invasion and
calphostin C was least effective in reducing adhesion molecule expression. Taken together,
PDT could be useful in the treatment of
gliomas but the choice of photosensitisers must be taken into consideration.