Estrogenic effects of genistein on the growth of estrogen receptor-positive human breast cancer (MCF-7) cells in vitro and in vivo.
Estrogenic effects of genistein on the growth of estrogen receptor-positive human breast cancer (MCF-7) cells in vitro and in vivo.
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发表时间：
1998-09
期刊：
影响因子：
11.2
通讯作者：
C. Hsieh;R. Santell;S. Haslam;W. Helferich
中科院分区：
文献类型：
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作者：
C. Hsieh;R. Santell;S. Haslam;W. Helferich
染料木黄酮，发现于豆制品中，是一种具有多种生物活性的植物化学物质。本课题主要研究染料木黄酮的雌激素样活性和增殖诱导活性。我们已经证明，染料木黄酮在低至10 nM的浓度下增强了体外雌激素依赖性人乳腺癌（MCF-7）细胞的增殖，100 nM的浓度达到与1 nM雌二醇相似的增殖效果。雌激素反应基因pS2的表达也被诱导在MCF-7细胞中，以响应低至1 μ M浓度的染料木黄酮的处理。在较高浓度（高于20 μ M）下，染料木黄酮抑制MCF-7细胞生长。在体内，我们已经表明，饮食治疗染料木黄酮（750 ppm）5天增强乳腺生长在28日龄卵巢切除无胸腺小鼠，表明染料木黄酮作为雌激素在正常乳腺组织。为了评价在体外观察到的MCF-7细胞的雌激素效应是否可以在体内重现，将MCF-7细胞皮下植入小鼠皮下。在卵巢切除的无胸腺小鼠中，每周测量雌激素依赖性肿瘤的生长。阴性对照动物接受美国营养研究所（AIN）-93G饮食，阳性对照组接受新的s.c.雌二醇（2 mg）颗粒加AIN-93 G饮食，第三组接受AIN-93 G饮食中的750 ppm染料木黄酮。染料木黄酮（750 ppm）处理组中的肿瘤比阴性对照组中的肿瘤更大，表明膳食染料木黄酮能够增强体内MCF-7细胞肿瘤的生长。在染料木素给药组中也观察到子宫重量增加。总之，染料木黄酮在体内和体外都可以作为雌激素激动剂，导致培养的人乳腺癌细胞（MCF-7）的增殖和诱导pS2基因的表达。在这里，我们提出了新的信息，饮食染料木黄酮刺激乳腺生长，并提高了MCF-7细胞肿瘤的卵巢切除无胸腺小鼠的生长。
Genistein, found in soy products, is a phytochemical with several biological activities. In the current study, our research focused on the estrogenic and proliferation-inducing activity of genistein. We have demonstrated that genistein enhanced the proliferation of estrogen-dependent human breast cancer (MCF-7) cells in vitro at concentrations as low as 10 nM, with a concentration of 100 nM achieving proliferative effects similar to those of 1 nM estradiol. Expression of the estrogen-responsive gene pS2 was also induced in MCF-7 cells in response to treatment with a concentration of genistein as low as 1 microM. At higher concentrations (above 20 microM), genistein inhibits MCF-7 cell growth. In vivo, we have shown that dietary treatment with genistein (750 ppm) for 5 days enhanced mammary gland growth in 28-day-old ovariectomized athymic mice, indicating that genistein acts as an estrogen in normal mammary tissue. To evaluate whether the estrogenic effects observed in vitro with MCF-7 cells could be reproduced in vivo, MCF-7 cells were implanted s.c. in ovariectomized athymic mice, and the growth of the estrogen-dependent tumors was measured weekly. Negative control animals received the American Institute of Nutrition (AIN)-93G diet, the positive control group received a new s.c. estradiol (2 mg) pellet plus the AIN-93G diet, and the third group received genistein at 750 ppm in the AIN-93G diet. Tumors were larger in the genistein (750 ppm)-treated group than they were in the negative control group, demonstrating that dietary genistein was able to enhance the growth of MCF-7 cell tumors in vivo. Increased uterine weights were also observed in the genistein-treated groups. In summary, genistein can act as an estrogen agonist in vivo and in vitro, resulting in the proliferation of cultured human breast cancer cells (MCF-7) and the induction of pS2 gene expression. Here we present new information that dietary genistein stimulates mammary gland growth and enhances the growth of MCF-7 cell tumors in ovariectomized athymic mice.