Allred C D, Allred K F, Ju Y H, Virant S M, Helferich W G
Department of Food Science and Human Nutrition, University of Illinois, Urbana, Illinois 61801, USA.
Cancer Res. 2001 Jul 1;61(13):5045-50.
We have demonstrated that the isoflavone, genistein, stimulates growth of estrogen-dependent human breast cancer (MCF-7) cells in vivo (C. Y. Hsieh et al., Cancer Res., 58: 3833-3838, 1998). The isoflavones are a group of phytoestrogens that are present in high concentrations in soy. Whether consumption of genistein from soy protein will have similar effects on estrogen-dependent tumor growth as pure genistein has not been investigated in the athymic mouse tumor implant model. Depending on processing, soy protein isolates vary widely in concentrations of genistein. We hypothesize that soy isolates containing different concentrations of genistein will stimulate the growth of estrogen-dependent cells in vivo in a dose-dependent manner. To test this hypothesis we conducted experiments in which these soy protein isolates were fed to athymic mice implanted s.c. with estrogen-dependent tumors. Genistein content (aglycone equivalent) of the soy isolate diets were 15, 150, or 300 ppm. Positive (with 17beta-estradiol pellet implant) and negative (no 17beta-estradiol) control groups received casein-based (isoflavone-free) diets. Tumor size was measured weekly. At completion of the study animals were killed and tumors collected for evaluation of cellular proliferation and estrogen-dependent gene expression. Incorporation of bromodeoxyuridine into cellular DNA was used as an indicator of cell proliferation, and pS2 mRNA was used as an estrogen-responsive gene. Soy protein diets containing varying amounts of genistein increased estrogen-dependent tumor growth in a dose-dependent manner. Cell proliferation was greatest in tumors of animals given estrogen or dietary genistein (150 and 300 ppm). Expression of pS2 was increased in tumors from animals consuming dietary genistein (150 and 300 ppm). Here we present new information that soy protein isolates containing increasing concentrations of genistein stimulate the growth of estrogen-dependent breast cancer cells in vivo in a dose-dependent manner.
我们已经证明，异黄酮染料木黄酮能在体内刺激雌激素依赖的人乳腺癌（MCF-7）细胞生长（C.Y. Hsieh等人，《癌症研究》，58: 3833 - 3838，1998）。异黄酮是一类植物雌激素，在大豆中含量很高。在无胸腺小鼠肿瘤植入模型中，尚未研究从大豆蛋白中摄入染料木黄酮是否会对雌激素依赖的肿瘤生长产生与纯染料木黄酮类似的影响。根据加工方式不同，大豆分离蛋白中染料木黄酮的浓度差异很大。我们假设，含有不同浓度染料木黄酮的大豆分离蛋白将以剂量依赖的方式在体内刺激雌激素依赖细胞的生长。为了验证这一假设，我们进行了实验，将这些大豆分离蛋白喂给皮下植入雌激素依赖肿瘤的无胸腺小鼠。大豆分离蛋白饮食中的染料木黄酮含量（苷元当量）为15、150或300 ppm。阳性（植入17β-雌二醇丸剂）和阴性（未植入17β-雌二醇）对照组接受基于酪蛋白的（不含异黄酮）饮食。每周测量肿瘤大小。研究结束时处死动物，收集肿瘤以评估细胞增殖和雌激素依赖基因表达。将溴脱氧尿苷掺入细胞DNA用作细胞增殖的指标，pS2 mRNA用作雌激素反应基因。含有不同量染料木黄酮的大豆蛋白饮食以剂量依赖的方式增加雌激素依赖肿瘤的生长。在给予雌激素或膳食染料木黄酮（150和300 ppm）的动物肿瘤中，细胞增殖最为显著。在食用膳食染料木黄酮（150和300 ppm）的动物肿瘤中，pS2的表达增加。在此，我们提供了新的信息，即含有浓度不断增加的染料木黄酮的大豆分离蛋白以剂量依赖的方式在体内刺激雌激素依赖的乳腺癌细胞生长。
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