Genistein stimulates growth of human breast cancer cells in a novel, postmenopausal animal model, with low plasma estradiol concentrations
Genistein stimulates growth of human breast cancer cells in a novel, postmenopausal animal model, with low plasma estradiol concentrations
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DOI：
10.1093/carcin/bgi370
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发表时间：
2006-06-01
期刊：
影响因子：
4.7
通讯作者：
Helferich, William G.
中科院分区：
文献类型：
--
作者：
Ju, Young H.;Allred, Kimberly F.;Helferich, William G.
We have demonstrated that genistein (GEN) stimulates growth of estrogen-dependent breast tumors in vivo. In this study, we evaluated whether dietary GEN can act in an additive manner with low circulating levels of 17 beta-estradiol (E-2).我们开发了一种使用硅橡胶植入物的 E-2 输送系统，其循环血浆 E-2 水平较低，与绝经后妇女中观察到的水平相似。我们插入不同浓度的 E-2 硅橡胶植入物（1:127、1:63、1:31、1:15 和 1:7 = E-2:胆固醇），并将雌激素依赖性人乳腺癌 (MCF-7) 细胞注射到卵巢切除的无胸腺小鼠中。测试的 E-2 植入物 (1:127-1:7) 在血浆中产生 30.1-101.6 pM E-2，与绝经后妇女中观察到的 E-2 水平相当。 The E-2 implants stimulated MCF-7 tumor growth in a dose-dependent manner.我们选择了 1:31 比例的 E-2 植入物来评估膳食 GEN 是否以低 E-2 水平的加性方式发挥作用，从而影响 MCF-7 肿瘤的生长。 Ovariectomized mice were divided into four groups: MCF-7 control, 500 ppm GEN, 1:31 E-2, and 1:31 E-2 + 500 ppm GEN.第 17 周时，这些组的平均肿瘤大小分别为 7.6、32.1、67.4 和 106.8 mm(2)（P < 0.05），表明在低水平 E-2 存在的情况下，500 ppm GEN 额外刺激了 MCF-7 肿瘤生长。 总之，我们建立了一个临床前小鼠模型，其 E-2 血液浓度与绝经后妇女中发现的相似。 Further, we observed that these concentrations regulate the growth rate of MCF-7 breast tumors.使用该模型，我们证明了膳食 GEN 在循环 E-2 水平较低的情况下以累加方式发挥作用，刺激体内雌激素依赖性肿瘤生长。这项研究的结果表明，对于患有雌激素依赖性乳腺癌的绝经后妇女来说，食用含有 GEN 的产品可能不安全。
We have demonstrated that genistein (GEN) stimulates growth of estrogen-dependent breast tumors in vivo. In this study, we evaluated whether dietary GEN can act in an additive manner with low circulating levels of 17 beta-estradiol (E-2). We developed an E-2 delivery system using silastic implants that yield low circulating plasma E-2 levels similar to those observed in postmenopausal women. We inserted various concentrations of E-2 silastic implants (1:127, 1:63, 1:31, 1:15 and 1:7 = E-2:cholesterol) and injected estrogen-dependent human breast cancer (MCF-7) cells into ovariectomized athymic mice. The E-2 implants tested (1:127-1:7) generated 30.1-101.6 pM E-2 in plasma, which is comparable to the E-2 levels observed in postmenopausal women. The E-2 implants stimulated MCF-7 tumor growth in a dose-dependent manner. We selected the 1:31 ratio of E-2 implant to evaluate if dietary GEN acts in an additive manner with low E-2 levels to influence the growth of MCF-7 tumors. Ovariectomized mice were divided into four groups: MCF-7 control, 500 ppm GEN, 1:31 E-2, and 1:31 E-2 + 500 ppm GEN. At week 17, the average tumor sizes were 7.6, 32.1, 67.4 and 106.8 mm(2) for these groups, respectively (P < 0.05), demonstrating that 500 ppm GEN additively stimulated MCF-7 tumor growth in the presence of low levels of E-2.In summary, we established a preclinical mouse model that results in E-2 blood concentrations similar to those found in postmenopausal women. Further, we observed that these concentrations regulate the growth rate of MCF-7 breast tumors. Using this model, we demonstrated that dietary GEN in the presence of low levels of circulating E-2 act in an additive manner to stimulate estrogen-dependent tumor growth in vivo. Results from this study suggest that consumption of products containing GEN may not be safe for postmenopausal women with estrogen-dependent breast cancer.