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金雀异黄素和大豆苷元可下调二氢睾酮在人前列腺LNCaP癌细胞中诱导的前列腺雄激素调节转录本-1(PART-1)基因表达。

Genistein and daidzein downregulate prostate androgen-regulated transcript-1 (PART-1) gene expression induced by dihydrotestosterone in human prostate LNCaP cancer cells.

作者信息

Yu Lunyin, Blackburn George L, Zhou Jin-Rong

机构信息

Nutrition/Metabolism Laboratory, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

出版信息

J Nutr. 2003 Feb;133(2):389-92. doi: 10.1093/jn/133.2.389.

Abstract

Epidemiologic investigations and laboratory studies suggest that bioactive soy phytochemical components may be used as an effective dietary regimen for prevention of prostate cancer. Studies designed to identify new genes that are responsive to androgens and are sensitive to the prevention of prostate cancer using soy bioactive components have become a research priority. In this study, we determined the effect of soy isoflavones on the expression of prostate androgen-regulated transcript 1 (PART-1), a newly discovered androgen-induced gene that may represent a novel androgen-dependent prostate cancer tumor marker. In an androgen-depleted cell culture system, 5alpha-dihydrotestosterone (DHT) induced expression of PART-1 transcript in androgen-sensitive LNCaP, but not in androgen-independent DU 145 or PC-3 human prostate cancer cells. The soy isoflavones genistein and daidzein dose-dependently inhibited DHT-induced expression of the PART-1 transcript. Genistein at 50 micro mol/L completely inhibited expression of the PART-1 transcript in LNCaP cells induced by DHT at 0.1 and 1.0 nmol/L. Daidzein was less potent than genistein, whereas glycitein at the same levels as genistein or daidzein did not inhibit DHT-induced PART-1 transcript expression. Our studies suggest that use of the PART-1 gene as a biomarker for evaluating the efficacy of soy isoflavones on androgen-dependent prostate cancer warrants further investigation.

摘要

流行病学调查和实验室研究表明,具有生物活性的大豆植物化学成分可作为预防前列腺癌的有效饮食方案。旨在鉴定对雄激素有反应且对大豆生物活性成分预防前列腺癌敏感的新基因的研究已成为研究重点。在本研究中,我们确定了大豆异黄酮对前列腺雄激素调节转录本1(PART-1)表达的影响,PART-1是一种新发现的雄激素诱导基因,可能代表一种新的雄激素依赖性前列腺癌肿瘤标志物。在雄激素缺乏的细胞培养系统中,5α-二氢睾酮(DHT)诱导雄激素敏感的LNCaP细胞中PART-1转录本的表达,但在雄激素非依赖性DU 145或PC-3人前列腺癌细胞中则不诱导。大豆异黄酮染料木黄酮和大豆苷元剂量依赖性地抑制DHT诱导的PART-1转录本的表达。50微摩尔/升的染料木黄酮完全抑制了0.1和1.0纳摩尔/升DHT诱导的LNCaP细胞中PART-1转录本的表达。大豆苷元的效力低于染料木黄酮,而与染料木黄酮或大豆苷元水平相同的黄豆黄素则不抑制DHT诱导的PART-1转录本表达。我们的研究表明,将PART-1基因用作评估大豆异黄酮对雄激素依赖性前列腺癌疗效的生物标志物值得进一步研究。

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