591 THE EFFECT OF PHOTOCHEMICAL INTERNALIZATION OF BLEOMYCIN IN THE TREATMENT OF UROTHELIAL CARCINOMA: AN IN VITRO STUDY

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You have accessJournal of UrologyBladder Cancer: Basic Research (I)1 Apr 2013591 THE EFFECT OF PHOTOCHEMICAL INTERNALIZATION OF BLEOMYCIN IN THE TREATMENT OF UROTHELIAL CARCINOMA: AN IN VITRO STUDY Harm C. Arentsen, Jos Falke, Anders Høgset, Egbert Oosterwijk, and J. Alfred Witjes Harm C. ArentsenHarm C. Arentsen Nijmegen, Netherlands More articles by this author , Jos FalkeJos Falke Nijmegen, Netherlands More articles by this author , Anders HøgsetAnders Høgset Oslo, Norway More articles by this author , Egbert OosterwijkEgbert Oosterwijk Nijmegen, Netherlands More articles by this author , and J. Alfred WitjesJ. Alfred Witjes Nijmegen, Netherlands More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1987AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Photochemical internalization (PCI) is a novel light-directed drug delivery system. It triggers the release of endocytosed drugs into the cytosol. Thus the drugs can reach their intracellular target of action, realizing their therapeutic potential, instead of being degraded by lysosomal hydrolases. The PCI effect is achieved with photosensitizing compounds specifically localized in the membranes of endocytic vesicles, destroying these membranes by an oxidative process after illumination. Bleomycin is used in multiple standard cancer chemotherapy regimens. The relatively large and hydrophilic chemical structure limits its ability to penetrate membranes, which causes accumulation in endocytic vesicles. PCI of bleomycin can induce a synergistic inhibition of tumor growth in different animal tumor models. In this in vitro study we determined whether meso-tetraphenyl chlorin disulphonate (TPCS2a)-based photochemical delivery of bleomycin was able to potentiate the cytotoxicity of bleomycin on bladder cancer cell lines. Epirubicin, gemcitabine and mitomycin C were used as controls. METHODS The human RT4, RT112, 253J, T24 and rat AY-27 urothelial carcinoma cell lines were used in this study. Cells were seeded in 96-well plates. TPCS2a was added to the growth medium and the plates were incubated overnight. Cells were then resuspended in TPCS2a-free culture medium and incubated for 3 h. Subsequently, cells were treated for 60 min with increasing doses of epirubicin, gemcitabine, mitomycin C or bleomycin followed by illumination for different periods (0-5 min) to obtain dose-response curves. Cell viability was measured with a colorimetric assay after 72 hours. RESULTS For the single treatments, in all five cell lines a dose dependent inhibition of cell proliferation was observed. This was seen both after treatment with TPCS2a-based PDT alone as well as after treatment with either bleomycin or one of the control chemotherapeutic agents alone. For the combination treatments, a significant (p<0,001) synergistic effect, i.e. photochemical internalization effect, was only observed for PDT combined with bleomycin in the human T24 cell line and the rat AY-27 cell line. CONCLUSIONS TPCS2a-based photochemical internalization of bleomycin showed a significant synergistic antiproliferative activity against human and rat urothelial carcinoma cells in vitro. Thus, PCI may have therapeutic potential as an intravesical strategy against NMIBC. Since the effect is heterogeneous, further animal studies to investigate the in vivo effects seem justified. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e242 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Harm C. Arentsen Nijmegen, Netherlands More articles by this author Jos Falke Nijmegen, Netherlands More articles by this author Anders Høgset Oslo, Norway More articles by this author Egbert Oosterwijk Nijmegen, Netherlands More articles by this author J. Alfred Witjes Nijmegen, Netherlands More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...