Differential effects of photofrin, 5-aminolevulinic acid and calphostin C on glioma cells.
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.
Au
Cheuk Man
CM
Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Yuk Choi Road, Hung Hom, Kowloon, Hong Kong S.A.R., People's Republic of China.
Luk
Sze Ki
SK
Jackson
Christopher John
CJ
Ng
Ho Keung
HK
Yow
Christine Miu Ngan
CM
To
Shing Shun Tony
SS
D000622:Aminolevulinic Acid / Q000494:pharmacology* / Q000633:toxicity; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D017323:Dihematoporphyrin Ether / Q000494:pharmacology* / Q000633:toxicity; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology* / Q000633:toxicity; D009361:Neoplasm Invasiveness / Q000473:pathology; D017319:Photosensitizing Agents / Q000494:pharmacology* / Q000633:toxicity
D015815:Cell Adhesion Molecules; D009281:Naphthalenes; D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid; D017323:Dihematoporphyrin Ether; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C058819:calphostin C