Photodynamic therapy of transitional cell carcinoma multicellular tumor spheroids with hypericin
The objective of the present study was to evaluate the sensitivity of the bladder transitional cell carcinoma (TCC) to hypericin PDT in a 3-D system using multicellular tumor spheroids. The photodynamic response in RT-112 human bladder TCC spheroids was also compared to 2-D cultured
monolayer cells. Following a 2-4 h incubation with 8-30 μM hypericin, spheroids or monolayer cells were irradiated at the light dose of 12 J/cm2, delivered at a fluence rate of 10-100 mW/cm2. The PDT effects were evaluated using a clonogenic assay. The results show that compared with the
cells in a monolayer, cells in spheroids were dramatically less sensitive to hypericin PDT (<2000-fold). Studies of fluorescence microphotographs of centrally cut frozen sections of hypericin-exposed spheroids showed a gradient in hypericin concentration from the peripheral to the central
region of the spheroid. Although it can be suggested that heterogeneity of drug uptake might be responsible for the observed resistance of spheroid to hypericin PDT, hypericin sensitized spheroids that were dissociated prior to light irradiation were as sensitive as the monolayer cells to
hypericin PDT, suggesting that other factors such as oxygen depletion might be responsible for the resistance of spheroids to hypericin PDT.
Document Type: Research Article
Affiliations: Laboratorium voor Farmaceutische Biologie en Fytofarmacologie, Faculteit Farmaceutische Wetenschappen, Katholieke Universiteit Leuven, Belgium
Publication date: 01 November 2003
- The International Journal of Oncology provides an international forum for the publication of the latest, cutting-edge research in the broad area of oncology and cancer treatment. The journal accepts original high quality works and reviews on all aspects of oncology research including carcinogenesis, metastasis, epidemiology, chemotherapy and viral oncology. Through fair and efficient peer review, the journal is dedicated to publishing top tier research in the field, offering authors rapid publication as well as high standards of copy-editing and production. The International Journal of Oncology is published on a monthly basis in both print and early online.
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