Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, Minnesota 55912, USA.
Pharm Res. 2012 Jun;29(6):1595-608. doi: 10.1007/s11095-012-0670-3. Epub 2012 Jan 27.
To test whether tanshinones inhibit prostate cancer (PCa) growth at least in part through inhibiting androgen receptor (AR) signaling.
We evaluated cell growth, survival and AR signaling parameters of PCa cells after exposure to tanshinones in in vitro models. We also tested the in vivo inhibitory efficacy of tanshinone IIA (TIIA) against LNCaP xenograft model in athymic nude mice.
For androgen-dependent LNCaP cells, a colony growth assay showed strong inhibitory potency following the order of TIIA≈cryptotanshinone>tanshinone I, being 10-30 folds higher than Casodex (racemic). TIIA inhibited growth of LNCaP cells more than several androgen-independent PCa cell lines. All 3 tested tanshinones were devoid of AR agonist activity under castrate condition. Mechanistically, tanshinones inhibited AR nuclear translocation within 2 h, decreased protein and mRNA abundance of AR and its target prostate-specific antigen within 12 h, and stimulated proteosomal degradation of AR. Oral administration of TIIA (25 mg/kg, once daily) retarded LNCaP xenograft growth and down-regulated tumor AR abundance in athymic nude mice.
AR targeting action of tanshinones was distinct from Casodex and contributed to prostate cancer growth suppression in vitro and in vivo.
检测丹参酮是否通过抑制雄激素受体（AR）信号通路，至少部分抑制前列腺癌（PCa）的生长。
我们在体外模型中评估了丹参酮暴露后 PCa 细胞的生长、存活和 AR 信号参数。我们还在裸鼠中测试了丹参酮 IIA（TIIA）对 LNCaP 异种移植模型的体内抑制效果。
对于雄激素依赖性的 LNCaP 细胞，集落生长试验显示 TIIA≈隐丹参酮>丹参酮 I 的抑制活力很强，比 Casodex（外消旋体）高 10-30 倍。TIIA 对 LNCaP 细胞的生长抑制作用强于几种雄激素非依赖性的 PCa 细胞系。在去势条件下，3 种测试的丹参酮均无 AR 激动剂活性。在机制上，丹参酮在 2 小时内抑制 AR 核易位，在 12 小时内降低 AR 及其靶标前列腺特异性抗原的蛋白和 mRNA 丰度，并刺激 AR 的蛋白体降解。口服 TIIA（25mg/kg，每日一次）可延缓 LNCaP 异种移植瘤的生长，并降低裸鼠中肿瘤 AR 的丰度。
丹参酮对 AR 的靶向作用与 Casodex 不同，可在体外和体内抑制前列腺癌的生长。
