姜黄素对LNCaP异种移植物中雄激素受体与Wnt/β-catenin相互作用的影响。

Korean Journal of Urology Pub Date : 2015-09-01 Epub Date: 2015-08-31 DOI:10.4111/kju.2015.56.9.656
Jeong Hee Hong, Gilho Lee, Han Yong Choi
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引用次数: 20

摘要

目的:姜黄素是一种无毒的化学预防剂,具有多方面的作用。我们之前的研究表明,姜黄素通过调节LNCaP细胞的Wnt/β-catenin信号通路抑制雄激素受体(AR)。因此,我们利用LNCaP异种移植物研究姜黄素在体内的作用。材料与方法:采用Balb/c裸鼠皮下接种LNCaP细胞。当肿瘤体积大于100 mm(3)时,每周口服姜黄素(500 mg/kg体重)或对照剂3次,持续4周。观察AR及Wnt/β-catenin中间产物的表达情况。结果:姜黄素在早期对肿瘤生长有抑制作用,随着时间的推移,肿瘤生长缓慢增加。姜黄素组肿瘤生长延迟约27%。姜黄素组的平均前列腺特异性抗原(PSA)翻倍时间约为未治疗组的两倍。姜黄素在mRNA和蛋白水平上显著降低AR的表达。姜黄素组的PSA水平有降低的趋势。然而,Wnt/β-catenin通路中间体的表达没有明显变化。结论:本研究表明,姜黄素最初通过抑制AR活性并可能通过降低PSA表达来干扰前列腺癌的生长。姜黄素的抗雄激素作用机制有待进一步研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Effect of curcumin on the interaction between androgen receptor and Wnt/β-catenin in LNCaP xenografts.

Purpose: Curcumin is a nontoxic, chemopreventive agent possessing multifaceted functions. Our previous study showed that curcumin inhibits androgen receptor (AR) through modulation of Wnt/β-catenin signaling in LNCaP cells. Therefore, we investigated the in vivo effects of curcumin by using LNCaP xenografts.

Materials and methods: LNCaP cells were subcutaneously inoculated in Balb/c nude mice. When the tumor volume reached greater than 100 mm(3), either curcumin (500 mg/kg body weight) or vehicle was administered through oral gavage three times weekly for 4 weeks. The expression of AR and intermediate products of Wnt/β-catenin were assessed.

Results: Curcumin had an inhibitory effect on tumor growth during the early period, which was followed by a slow increase in growth over time. Tumor growth was delayed about 27% in the curcumin group. The mean prostate-specific antigen (PSA) doubling time in the curcumin group was approximately twice that in the untreated group. Curcumin significantly decreased AR expression at both the mRNA and protein level. The PSA levels tended to be reduced in the curcumin group. However, there were no significant changes in expression of Wnt/β-catenin pathway intermediates.

Conclusions: This study revealed that curcumin initially interferes with prostate cancer growth by inhibiting AR activity and possibly by reducing PSA expression. Further research is needed to investigate the plausible mechanism of the antiandrogenic action of curcumin.

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