Resistance to cisplatin (CDDP)-based combination therapies makes advanced bladder cancer difficult to treat. UMUC3-control-short hairpin RNA (shRNA) cells with endogenous androgen receptor (AR) and AR-negative 647V/5637 cells stably expressing AR were more resistant to CDDP than UMUC-AR-shRNA and vector control cells, respectively. In AR-positive cells, treatment with R1881, a synthetic androgen, induced NF-κB expression (a mechanism of CDDP resistance). Furthermore, AR and NF-κB levels were increased in CDDP-resistant cells following long-term CDDP exposure. These data suggest that AR activation might be involved in CDDP resistance via a NF-κB mechanism, and that targeting AR might overcome CDDP resistance