Effect of ALA–mediated photodynamic therapy in combination with tumor necrosis factor–related apoptosis–inducing ligand (TRAIL) on bladder cancer cells

INTRODUCTION Photodynamic therapy (PDT), an alternative treatment modality for superficial bladder tumors is based on the interaction of a photosensitizer with light. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising candidate for anticancer therapy due to its ability to selectively induce apoptosis in cancer cells. However, not all tumor cells are sensitive to TRAIL. TRAIL-resistant cancer cells can be sensitized to TRAIL induced apoptosis by anticancer agents. OBJECTIVE We investigated the combined cytotoxic effect of TRAIL and PDT with 5-aminolevulinic acid (ALA) on bladder cancer cells. MATERIALS AND METHODS THREE HUMAN BLADDER TRANSITIONAL CANCER CELL LINES: T24, 647V, and SW780 were treated with TRAIL and/or ALA-mediated PDT. Cytotoxicity was determined by MTT and LDH assay. RESULTS Our study confirmed that T24 and 647V bladder cancer cells were resistant to TRAIL, whereas SW780 cells were sensitive to TRAIL. We therefore examined the cytotoxic effect of TRAIL in combination with ALA-mediated PDT on bladder cancer cells. We showed for the first time that pretreatment with low dose of PDT significantly sensitizes bladder cancer cells to TRAIL induced cytotoxicity. CONCLUSION ALA-mediated PDT augments the cytotoxic effect of TRAIL on transitional cancer cells of bladder. The obtained results suggest that combined treatment of TRAIL and PDT may provide the basis for a new strategy to induce cytotoxicity in bladder cancer cells.