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.


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.
Department of Urology, University Hospital, Mannheim, Germany.
Axel
A
Schaaf
Sreedhar
S
Sagi
Sigrun
S
Langbein
Lutz
L
Trojan
Peter
P
Alken
Maurice Stephan
MS
Michel
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity*; D002470:Cell Survival; D002945:Cisplatin / Q000494:pharmacology* / Q000633:toxicity*; D004347:Drug Interactions; D019254:Genes, bcl-2; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D013873:Thionucleotides; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000473:pathology*
D000970:Antineoplastic Agents; D016376:Oligonucleotides, Antisense; D013873:Thionucleotides; D002945:Cisplatin