Abstract

Background: Photodynamic therapy (PDT) is an attractive, emerging therapeutic procedure suitable for the treatment of non-muscle-invasive bladder cancer. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a death ligand that belongs to the TNF superfamily of cytokines. The ability of TRAIL to selectively induce apoptosis in cancer cells but not in normal cells promotes the development of TRAIL-based cancer therapy. However, many tumor cells are resistant to TRAIL-induced apoptosis. The purpose of the study was to overcome TRAIL-resistance in bladder cancer cells by photodynamic therapy (PDT).
Material/Methods: Three human bladder transitional cancer cell lines – T24, 647V and SW780 – were treated with TRAIL and/or chlorin-based PDT. The cytotoxicity was measured by MTT and LDH assays and apoptosis was detected using annexin V by flow cytometry.
Results: Our test confirmed that T24 and 647V bladder cancer cells are resistant to TRAIL, whereas SW780 cells are sensitive to TRAIL. Then we examined the cytotoxic and apoptotic effects of TRAIL in combination with chlorin e6-polyvinylpyrrolidone (Ce6-PVP)-mediated PDT on bladder cancer cells. We showed for the first time that pretreatment with a low dose of PDT significantly sensitizes bladder cancer cells to TRAIL-induced apoptosis. Chlorin-based PDT augments the effect of TRAIL on bladder cancer cells.
Conclusions: PDT with Ce6-PVP photosensitizer enhances the cytotoxic and apoptotic effects of TRAIL on bladder cancer cells. The obtained results suggest that combined treatment by TRAIL and PDT may provide the basis for a new therapeutic approach to induce cell death in bladder cancer.

Keywords: TNF-Related Apoptosis-Inducing Ligand - therapeutic use, Porphyrins - therapeutic use, Photochemotherapy - methods, L-Lactate Dehydrogenase - metabolism, Annexin A5, Analysis of Variance, Tetrazolium Salts, Thiazoles, Urinary Bladder Neoplasms - drug therapy