Department of Urology, First People's Hospital Affiliated to Shanghai, Jiao Tong University, Shanghai, China.
Urology. 2010 Apr;75(4):820-7. doi: 10.1016/j.urology.2009.10.041. Epub 2010 Jan 18.
To investigate whether androgen receptor (AR) could serve as a potential molecular target for the treatment of bladder cancer.
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.
AR expression knockdown produced increased apoptosis, decreased proliferation, and migration of bladder cancer cells. Cyclin D1, Bcl-x(L), 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.
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.
探讨雄激素受体（AR）能否成为膀胱癌治疗的潜在分子靶点。
用靶向 AR 的小干扰 RNA 处理人移行细胞癌细胞系 T24 和 253-J，检测细胞增殖、凋亡和迁移能力，采用定量逆转录聚合酶链反应评估与生长和转移相关基因的表达水平。在接受电穿孔辅助抗-AR 小干扰 RNA 给药的 T24 荷瘤裸鼠体内，评估肿瘤细胞生长和凋亡情况。
AR 表达下调可导致膀胱癌细胞凋亡增加、增殖和迁移减少。AR 敲低后，细胞周期蛋白 D1、Bcl-x(L)和基质金属蛋白酶-9 基因表达也减少，这可能导致癌细胞生物学行为改变。体内实验表明，通过电穿孔辅助的干扰使 AR 表达沉默，可显著抑制 AR 阳性膀胱癌肿瘤的生长，降低细胞增殖，增加凋亡率。
下调 AR 表达可抑制膀胱癌细胞的体外和体内生长，表明其可能成为膀胱癌治疗的潜在治疗靶点。
