一种雄激素非依赖性雄激素受体功能可保护PC3/PC3(AR)前列腺癌细胞系免受肌醇六磷酸毒性的影响。

An androgen-independent androgen receptor function protects from inositol hexakisphosphate toxicity in the PC3/PC3(AR) prostate cancer cell lines.

作者信息

Diallo Jean-Simon, Péant Benjamin, Lessard Laurent, Delvoye Nathalie, Le Page Cécile, Mes-Masson Anne-Marie, Saad Fred

机构信息

Centre de recherche du Centre hospitalier de l'Université de Montréal (CR-CHUM) and Institut du cancer de Montréal, Montreal, Quebec, Canada.

出版信息

Prostate. 2006 Sep 1;66(12):1245-56. doi: 10.1002/pros.20455.

DOI:10.1002/pros.20455

PMID:16705740

Abstract

BACKGROUND

Inositol hexakisphosphate (IP6) is a phytochemical exhibiting anticancer activity. Because few prostate cancer (PCa) cell lines have been used to study IP6, we assessed its efficacy in a panel of PCa cell lines.

METHODS AND RESULTS

Using WST-1 assays we observed that, although androgens did not modulate its efficacy, IP6 was more active in androgen receptor (AR) negative cells than in AR-positive cells. Stable expression of the AR in PC3 cells (PC3(AR)) decreased the response to IP6, which was reversed by an AR-targeting siRNA. Furthermore, AR expression in PC3 cells resulted in significantly reduced caspase-3 activation (P < 0.001) and DNA fragmentation (P < 0.05) in response to IP6. Similarly, although treatment with IP6 caused the upregulation of NF-kappaB-responsive (IkappaB-alpha, IRF-2) and p53/E2F-responsive genes (Puma, Noxa) in PC3 cells, this increase was reduced in PC3AR cells (P < 0.01).

CONCLUSION

We conclude that resistance to IP6 can be linked to a ligand-independent AR function.

摘要

背景

肌醇六磷酸（IP6）是一种具有抗癌活性的植物化学物质。由于很少有前列腺癌细胞系用于研究IP6，我们评估了其在一组前列腺癌细胞系中的疗效。

方法与结果

使用WST-1检测，我们观察到，虽然雄激素不调节其疗效，但IP6在雄激素受体（AR）阴性细胞中比在AR阳性细胞中更具活性。在PC3细胞（PC3(AR)）中稳定表达AR可降低对IP6的反应，而靶向AR的siRNA可逆转这种反应。此外，PC3细胞中的AR表达导致对IP6反应时caspase-3激活（P < 0.001）和DNA片段化（P < 0.05）显著降低。同样，虽然用IP6处理导致PC3细胞中NF-κB反应性（IκB-α、IRF-2）和p53/E2F反应性基因（Puma、Noxa）上调，但在PC3AR细胞中这种增加减少（P < 0.01）。