A role for SIRT1 in cell growth and chemoresistance in prostate cancer PC3 and DU145 cells.
SIRT1, which belongs to the family of type III histone deacetylase, is implicated in diverse cellular processes. We have determined the expression levels of SIRT1 in human prostate cancer cell lines and have examined the roles of SIRT1 in cell growth and chemoresistance. SIRT1 expression was markedly up-regulated in androgen-refractory PC3 and DU145 cells compared with androgen-sensitive LNCaP cells and its expression level was correlated with cell growth in PC3 cells. Treatment with a SIRT1 inhibitor, sirtinol, inhibited cell growth and increased sensitivity to camptothecin and cisplatin. Silencing of SIRT1 expression by siRNA also suppressed cell proliferation and reduced camptothecin resistance in PC3 cells, mimicking the chemosensitizing effect caused by sirtinol. Also in DU145 cells, sirtinol treatment enhanced sensitivity to camptothecin and cisplatin. These results suggest that up-regulation of SIRT1 expression may play an important role in promoting cell growth and chemoresistance in androgen-refractory PC3 and DU145 cells.
Department of Urology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, Gifu 501-1193, Japan.
Keitaro
K
Kojima
Riyako
R
Ohhashi
Yasunori
Y
Fujita
Nanako
N
Hamada
Yukihiro
Y
Akao
Yoshinori
Y
Nozawa
Takashi
T
Deguchi
Masafumi
M
Ito
D000728:Androgens / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D002166:Camptothecin / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D008297:Male; D009284:Naphthols / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000201:enzymology*; D056564:Sirtuin 1; D037761:Sirtuins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D000728:Androgens; D000970:Antineoplastic Agents; D001549:Benzamides; D009284:Naphthols; C439060:sirtinol; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D037761:Sirtuins; D002945:Cisplatin; D002166:Camptothecin