Accumulation of protoporphyrin IX in medulloblastoma cell lines and sensitivity to subsequent photodynamic treatment

摘要: Summary Background Medulloblastoma (MB) is the most common malignant primary brain tumor of childhood. High risk patients still have a poor outcome, and especially young suffer from standard therapy induced sequelae. Therefore, other therapeutic options need to be explored. In glioblastoma (GBM), application 5-aminolaevulinic acid (5-ALA) results in selective accumulation protoporphyrin IX (PPIX) cells, which can exploited during fluorescence-guided surgery increase extent resection or for photodynamic (PDT) phototoxicity. It not entirely clear, whether MB cells accumulate PPIX are sensitive PDT. Methods Human MYC-amplified (Med8A D283) non-amplified (UW228–2 ONS76) cell lines were incubated 2, 4 6 h with increasing doses (0–100 μg/ml) 5-ALA, was determined by flow cytometry. To assess sensitivity 5-ALA/PDT, 5-ALA subsequently exposed laser light 635 nm wavelength (18.75 J/cm2). After an additional 24 h culture period, viability quantified using WST-1 assay. Expression ferrochelatase detected reverse transcription quantitative polymerase chain reaction. Ferrochelatase activity measuring enzymatic conversion zinc-protoporphyrin. ABCG2 transporter protein CD338 Results All showed time- dose-dependent after exposure exogenous became 5-ALA/PDT-induced reduced compared U373 GBM at shorter incubation periods limiting doses. Moreover, all positive overall phototoxicity lower lines. Notably, demonstrated more pronounced photosensitivity their counterparts. There no difference expression ferrochelatase, but appeared whereas expressed on only. Conclusion become PDT, associated low activity. Photosensitivity contrast however, appears reduced, restricted subset lines, possibly due cells.