Chuu Chih-Pin, Chen Rou-Yu, Hiipakka Richard A, Kokontis John M, Warner Karen V, Xiang Jialing, Liao Shutsung
The Ben May Department for Cancer Research, The University of Chicago, CIS W325F, 929 E. 57th Street, Chicago, IL 60637, USA.
Biochem Biophys Res Commun. 2007 Jun 1;357(2):341-6. doi: 10.1016/j.bbrc.2007.03.116. Epub 2007 Mar 28.
T0901317 is a potent non-steroidal synthetic liver X receptor (LXR) agonist. T0901317 blocked androgenic stimulation of the proliferation of androgen-dependent LNCaP 104-S cells and androgenic suppression of the proliferation of androgen-independent LNCaP 104-R2 cells, inhibited the transcriptional activation of an androgen-dependent reporter gene by androgen, and suppressed gene and protein expression of prostate specific antigen (PSA), a target gene of androgen receptor (AR) without affecting gene and protein expression of AR. T0901317 also inhibited binding of a radiolabeled androgen to AR, but inhibition was much weaker compared to the effect of the antiandrogens, bicalutamide and hydroxyflutamide. The LXR agonist T0901317, therefore, acts as an antiandrogen in human prostate cancer cells.
T0901317是一种强效非甾体类合成肝X受体（LXR）激动剂。T0901317可阻断雄激素对雄激素依赖性LNCaP 104-S细胞增殖的刺激作用以及雄激素对雄激素非依赖性LNCaP 104-R2细胞增殖的抑制作用，抑制雄激素对雄激素依赖性报告基因的转录激活，并抑制雄激素受体（AR）的靶基因前列腺特异性抗原（PSA）的基因和蛋白表达，而不影响AR的基因和蛋白表达。T0901317还可抑制放射性标记雄激素与AR的结合，但与抗雄激素药物比卡鲁胺和羟基氟他胺相比，其抑制作用要弱得多。因此，LXR激动剂T0901317在人前列腺癌细胞中可作为一种抗雄激素发挥作用。
