Androgen Receptor Is a Potential Therapeutic Target for Bladder Cancer

OBJECTIVES To investigate whether androgen receptor (AR) could serve as a potential molecular target for the treatment of bladder cancer. METHODS Cell proliferation, apoptosis, and migration capacity were determined in human transitional carcinoma cell lines T24 and 253-J treated with small interfering RNA directed against AR, and expression levels of growth- and metastasis-related genes were assessed using quantitative reverse transcriptase-polymerase chain reaction. Tumor cell growth and apoptosis were also evaluated in vivo in T24 tumor-bearing nude mice receiving electroporation-assisted administration of anti-AR small interfering RNA. RESULTS AR expression knockdown produced increased apoptosis, decreased proliferation, and migration of bladder cancer cells. Cyclin D1, Bcl-xL, and matrix metallopeptidase-9 gene expression were also reduced with AR knockdown, which might have contributed to the altered biological behavior of cancer cells. In vivo experiments showed that silencing AR expression, by interference aided by electroporation, significantly suppressed AR-positive bladder tumor growth with decreased cell proliferation and increased apoptotic rates. CONCLUSIONS Downregulation of AR expression inhibits bladder cancer cell growth in vitro and in vivo, implying that its use might be a potential therapeutic target for the treatment of bladder cancer. UROLOGY 75: 820-827, 2010. (C) 2010 Elsevier Inc.