Cytotoxicity of cisplatin in bladder cancer is significantly enhanced by application of bcl-2 antisense oligonucleotides

Background: The aim of our study was to examine the effects of the combined application of cisplatin and bcl-2 antisense oligonucleotide on human bladder cancer cell lines to determine the possible synergistic effects in cytotoxicity and to estimate its potential value for subsequent in vivo trials. Materials and Methods: Human bladder cancer cell lines (UM-UC 3, RT 112, T24/83 and HT 1197) were treated with bcl-2 antisense oligonucleotide, cisplatin, or a combination of both and incubated for 48 h under standard conditions. Cell survival was determined using a Neubauer haemocytometer or standard MTT assay. BCL-2 expression was verified using western blotting. Results: The combined treatment resulted in significant lower cell survival rates compared to individual treatment. Additionally, there was a decrease in cell survival rate with an increase in cisplatin concentration in combined treatment that was not observed in cisplatin mono treatment. Conclusions: For the combined treatment with oligonucleotides and cisplatin a synergistic effect can be strongly suggested. Therefore, further investigations and in vivo trials have to be done to determine the possible benefits for clinical applications. (C) 2004 Elsevier Inc. All rights reserved.