Journal of Carcinogenesis, 2007, 6(1):3.

Genistein chemoprevention of prostate cancer in TRAMP mice

Jun Wang, Coral A Lamartiniere，et al

Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL, USA; et al

Epidemiological studies suggest an inverse association between soy intake and prostate cancer risk. Genistein, the predominant phytoestrogen in soy food, has been proposed as a potential chemopreventive agent due to its anti-estrogen and tyrosine kinase inhibitory effects. To determine the most effective period for genistein chemoprevention, the Transgenic adenocarcinoma mouse prostate (TRAMP) model was used. The treatments were 250 mg genistein/kg AIN-76A diet 1) prepubertally only, 2) in adulthood only or 3) through out life. Controls received AIN-76A diet. By 28 weeks of age, 100% TRAMP mice fed control diet developed prostatic intraepithelial neoplasia (PIN) or adenocarcinomas with 6%, 16%, 44% and 34% developing high grade PIN, well differentiated, moderately differentiated and poorly differentiated prostatic adenocarcinomas, respectively. Prepubertal only (1-35 days postpartum) and adult only genistein treatments (12-28 weeks) resulted in 6% and 29% decreases in poorly-differentiated cancerous lesions compared with controls, respectively. The most significant effect was seen in the TRAMP mice exposed to genistein throughout life (1-28 weeks) with a 50% decrease in poorly-differentiated cancerous lesions. In a separate experiment in castrated TRAMP mice, dietary genistein suppressed the development of advanced prostate cancer by 35% compared with controls. Of the tumors that developed in castrated TRAMP mice, 100% were poorly-differentiated in contrast to the 37% of noncastrated TRAMP mice that developed poorly-differentiated tumors. ICI 182,780 (ICI), genistein and estrogen down-regulated androgen receptor (AR), estrogen receptor alpha (ER-alpha) and progesterone receptor (PR) in the prostates of C57BL/6 mice, and act independently of ER. Our data obtained in intact and castrated transgenic mice suggest that genistein may be a promising chemopreventive agent against androgen-dependent and independent prostate cancers.

英国《致癌学杂志》，2007年

金雀异黄素在TRAMP小鼠中化学预防前列腺癌

王俊，库欧 A 拉曼提尼尔，等

阿拉巴马大学药理学与毒理学系，伯明翰，美国; 等

流行病学研究表明大豆摄入和前列腺癌风险之间存在负相关。染料木黄酮，主要的植物雌激素在大豆食品中，由于其抗雌激素和酪氨酸激酶抑制作用，已被提出作为潜在的化学预防剂。至确定染料木素化学预防的最有效期，使用转基因腺癌​​小鼠前列腺（TRAMP）模型。治疗方法是250mg染料木素/ kg AIN-76A饮食1）预先制定，2）仅在成年期或3）通过生命。收到的控制AIN-76A饮食。通过28周龄，100％TRAMP小鼠喂食对照饮食发展为前列腺上皮内瘤变（PIN）或腺癌6％，16％，44％和34％发展高品位PIN，高分化，中等分化和分化不良的前列腺腺癌。只有早产（产后1-35天）和成人只有染料木素治疗（12-28周）导致6％和与对照组相比，分化不良的癌性病变分别降低29％。最显着的效果是在TRAMP小鼠在生命中（1-28周）暴露于染料木素，分化不良的癌性病变减少50％。在一个单独的在阉割的TRAMP小鼠中，饮食染料木素与前列腺癌相比，抑制了晚期前列腺癌的发展控制。在阉割的TRAMP小鼠中发育的肿瘤中，100％的细胞分化不良，37％的未刺激发展较差分化肿瘤的TRAMP小鼠。 ICI 182,780（ICI），染料木素和雌激素下调雄激素受体（AR）C57BL / 6小鼠前列腺中的雌激素受体α（ER-α）和孕激素受体（PR），独立于ER起作用。我们的资料在完整和阉割的转基因小鼠中获得的结果表明，对于依赖和独立的前列腺癌，染料木素可能是一种有希望的化学预防剂。