Suppressed tumour growth and enhanced chemosensitivity by RNA interference targeting Aurora-A in the PC3 human prostate cancer model.
OBJECTIVE
To investigate the inhibitory effects of Aurora-A expression in prostate cancer cells on their growth and chemosensitivity.


METHODS
Aurora-A expression in radical prostatectomy specimens obtained from 193 patients were evaluated by immunohistochemical staining. We then established PC3 cells in which the expression vector containing short-hairpin RNA (shRNA) targeting Aurora-A was introduced (PC3/sh-A). The growth and the sensitivity to docetaxel in PC3/sh-A were compared with those in PC3 transfected with control vector alone (PC3/C).


RESULTS
Immunohistochemistry showed that there were various levels of Aurora-A expression in most prostate cancer tissues, and the expression levels of Aurora-A in prostate cancer were significantly related to Gleason score. Expression levels of both Aurora-A mRNA and protein in PC3/sh-A were approximately 20% of those in PC3/C. In vitro growth of PC3/sh-A was significantly worse than that of PC3/C, and the proportion of PC3/sh-A in the G2-M phase was significantly greater than that of PC3/C. The 50% inhibitory concentration of docetaxel in PC3/sh-A decreased by 67% compared with that in PC3/C. Tumour volume in nude mice injected with PC3/sh-A was significantly smaller than that with PC3/C. Furthermore, treatment of nude mice bearing PC3/sh-A tumour with docetaxel (10 mg/kg, once weekly for 4 weeks) achieved a synergistic cytotoxic effect, despite the lack of an enhanced antitumour effect of docetaxel on PC3/C tumours.


CONCLUSIONS
The suppression of Aurora-A using shRNA could be a useful therapeutic strategy against androgen-independent prostate cancer, through growth inhibition as well as enhanced chemosensitivity.
Kumano
Masafumi
M
Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan.
Miyake
Hideaki
H
Terakawa
Tomoaki
T
Furukawa
Junya
J
Fujisawa
Masato
M
D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D064096:Aurora Kinase A; D064127:Aurora Kinases; D000077143:Docetaxel; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D034622:RNA Interference; D043823:Taxoids / Q000494:pharmacology*; D047368:Tumor Burden; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D043823:Taxoids; D000077143:Docetaxel; C576918:Aurka protein, mouse; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases