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首页> 外文期刊>The Journal of Nutritional Biochemistry >Pomegranate polyphenols down-regulate expression of androgen-synthesizing genes in human prostate cancer cells overexpressing the androgen receptor
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Pomegranate polyphenols down-regulate expression of androgen-synthesizing genes in human prostate cancer cells overexpressing the androgen receptor

机译：石榴多酚下调雄激素受体过表达的人前列腺癌细胞中雄激素合成基因的表达

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摘要

Prostate cancer is dependent on circulating testosterone in its early stages and is treatable with radiation and surgery. However, recurrent prostate tumors advance to an androgen-independent state in which they progress in the absence of circulating testosterone, leading to metastasis and death. During the development of androgen independence, prostate cancer cells are known to increase intracellular testosterone synthesis, which maintains cancer cell growth in the absence of significant amounts of circulating testosterone. Overexpression of the androgen receptor (AR) occurs in androgen-independent prostate cancer and has been proposed as another mechanism promoting the development of androgen independence. The LNCaP-AR cell line is engineered to overexpress AR but is otherwise similar to the widely studied LNCaP cell line. We have previously shown that pomegranate extracts inhibit both androgen-dependent and androgen-independent prostate cancer cell growth. In this study, we examined the effects of pomegranate polyphenols, ellagitannin-rich extract and whole juice extract on the expression of genes for key androgen-synthesizing enzymes and the AR. We measured expression of the HSD3B2 (3o-hydroxysteroid dehydrogenase type 2), AKR1C3 (aldo-keto reductase family 1 member C3) and SRD5A1 (steroid 5l reductase type 1) genes for the respective androgen-synthesizing enzymes in LNCaP, LNCaP-AR and DU-145 human prostate cancer cells. A twofold suppression of gene expression was considered statistically significant. Pomegranate polyphenols inhibited gene expression and AR most consistently in the LNCaP-AR cell line (P=.05). Therefore, inhibition by pomegranate polyphenols of gene expression involved in androgen-synthesizing enzymes and the AR may be of particular importance in androgen-independent prostate cancer cells and the subset of human prostate cancers where AR is up-regulated.
机译：前列腺癌在早期依赖循环睾丸激素，可以通过放射和手术治疗。然而，复发性前列腺肿瘤发展为雄激素非依赖性状态，在这种状态下，它们在缺乏循环睾丸激素的情况下进展，导致转移和死亡。在雄激素独立性的发展过程中，已知前列腺癌细胞会增加细胞内睾丸激素的合成，从而在没有大量循环睾丸激素的情况下维持癌细胞的生长。雄激素受体（AR）的过表达发生在非雄激素依赖性前列腺癌中，并已被提议为促进雄激素非依赖性发展的另一种机制。 LNCaP-AR细胞系经工程改造可过表达AR，但与广泛研究的LNCaP细胞系相似。先前我们已经表明，石榴提取物抑制雄激素依赖性和非雄激素依赖性前列腺癌细胞的生长。在这项研究中，我们检查了石榴多酚，富含鞣花单宁的提取物和全汁提取物对关键雄激素合成酶和AR基因表达的影响。我们在LNCaP，LNCaP-AR和LNCaP，LNCaP-AR和LNCaP，LNCaP-AR和LNCaP，LNCaP-AR和DU-145人前列腺癌细胞。基因表达的双重抑制被认为具有统计学意义。石榴多酚在LNCaP-AR细胞系中最一致地抑制基因表达和AR（P = .05）。因此，石榴多酚对涉及雄激素合成酶和AR的基因表达的抑制在不依赖雄激素的前列腺癌细胞和AR被上调的人前列腺癌的子集中可能特别重要。

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