Anti-tumor effect of small interfering RNA targeting the androgen receptor in human androgen-independent prostate cancer cells.
Early phase prostate cancer is usually androgen-dependent, with the androgen/androgen receptor (AR) signaling pathway playing a central role. At this stage, the cancer responds well to androgen ablation therapy, but prostate cancers eventually acquire androgen independence and more aggressive phenotypes. Several studies, however, have shown that the majority of tumors still express functional AR, which is often amplified and mutated. To determine if the AR is a plausible therapeutic target, we investigated the anti-tumor effect of small interfering RNAs targeting the AR (siAR) in the human prostate cancer cells, LNCaP and 22Rv1, which express mutated AR. In both types of cells, transfection of siAR suppressed mutated AR expression and significantly reduced cell growth. Furthermore, atelocollagen-mediated systemic siAR administration markedly inhibited the growth of 22Rv1 cells subcutaneously xenografted in castrated nude mice. These results suggest that the AR is still a key therapeutic target even in androgen-independent prostate cancer (AIPC). Silencing of AR expression in AIPC opens promising therapeutic perspectives.
Azuma
Koji
K
Department of Urology, Ehime University Graduate School of Medicine, 454 Shitsukawa, Toon, Ehime 791-0295, Japan.
Nakashiro
Koh-ichi
K
Sasaki
Toyokazu
T
Goda
Hiroyuki
H
Onodera
Jun
J
Tanji
Nozomu
N
Yokoyama
Masayoshi
M
Hamakawa
Hiroyuki
H
D059002:Androgen Receptor Antagonists; D000728:Androgens / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D045744:Cell Line, Tumor; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000628:therapy*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*; D011944:Receptors, Androgen / Q000235:genetics
D059002:Androgen Receptor Antagonists; D000728:Androgens; D034741:RNA, Small Interfering; D011944:Receptors, Androgen