OBJECTIVES: To investigate the inhibitory effects of Aurora-A expression in prostate cancer cells on their growth and chemosensitivity. PATIENTS AND 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.
OBJECTIVES: To investigate the inhibitory effects of Aurora-A expression in prostate cancer cells on their growth and chemosensitivity. PATIENTS AND 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.
Authors: Yi Gong; Yanli Li; Yin Lu; Linglin Li; Hamid Abdolmaleky; George L Blackburn; Jin-Rong Zhou Journal: Int J Cancer Date: 2010-11-03 Impact factor: 7.396
Authors: Kati Kivinummi; Alfonso Urbanucci; Katri Leinonen; Teuvo L J Tammela; Matti Annala; William B Isaacs; G Steven Bova; Matti Nykter; Tapio Visakorpi Journal: Sci Rep Date: 2017-12-21 Impact factor: 4.379