Figure 4.

Chemoresistant bladder cancer cell lines can be sensitized to chemotherapeutics by epigenetic modifiers. (A) Treatment with the epigenetic inhibitors decitabine and vorinostat significantly lowers IC₅₀ values for cisplatin in the resistant bladder cancer cell lines 96-1, 97-1, RT4 and SW1710. Cell lines were treated with 100 nM decitabine, 100 nM vorinostat, 100 nM decitabine + vorinostat or vehicle (DMSO) for 120 h, incubated with cisplatin for 48 h and then cisplatin IC₅₀ values were calculated. The graph shows fold compound reduction to vehicle. Experiments were run in triplicates to obtain mean IC₅₀ values; (B) Decitabine and vorinostat induce sensitization for doxorubicin, etoposide and vinblastine in the cisplatin resistant bladder cancer cell lines 96-1 (top) and RT4 (bottom). Cell lines were treated with 100 nM decitabine, 100 nM vorinostat, 100 nM decitabine + vorinostat or vehicle for 120 h, incubated with cisplatin for 48 h and then cisplatin IC₅₀ values were calculated. The graph shows IC_50(vehicle)/IC_50(post-AZA). Experiments were run in triplicates to obtain mean IC₅₀ values. 5-AZA-CdR: decitabine; SAHA: vorinostat.