The effect of photochemical internalization of bleomycin in the treatment of urothelial carcinoma of the bladder: an in vitro study

OBJECTIVES: 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 cells. MATERIALS AND METHODS: The human RT4, RT112, 253J, T24, and rat AY-27 urothelial carcinoma cell lines were used. 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 hours. Subsequently, cells were treated for 60 minutes with increasing doses of epirubicin, gemcitabine, mitomycin C, or bleomycin followed by illumination for different periods. Cell viability was measured with a colorimetric assay after 72 hours. RESULTS: For the single treatments, in all 5 cell lines a dose-dependent inhibition of cell proliferation was observed. This was seen both after treatment with TPCS2a-based photodynamic therapy (PDT), as well as after treatment with either bleomycin or one of the control chemotherapeutic agents. After treatment with PDT (240-s illumination), bleomycin 9.0 microM, and the combination of these treatments, relative survival percentages were 89.2 +/- 13.0, 70.2 +/- 8.9, and 30.5 +/- 6.1, respectively, in the T24 cell line. After treatment with PDT (120-s illumination), bleomycin 27 microM and the combination of these treatments, relative survival percentages were 93.6 +/- 15.7, 74.7 +/- 9.6, and 30.0 +/- 11.1, respectively, in the AY-27 cell line. In both cell lines, PDT combined with bleomycin showed significantly (P