Soy phytochemicals synergistically enhance the preventive effect of tamoxifen on the growth of estrogen-dependent human breast carcinoma in
Soy phytochemicals synergistically enhance the preventive effect of tamoxifen on the growth of estrogen-dependent human breast carcinoma in
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DOI：
10.1093/carcin/bgm004
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发表时间：
2007-06-01
期刊：
影响因子：
4.7
通讯作者：
Zhou, Jin-Rong
中科院分区：
文献类型：
--
作者：
Mai, Zhiming;Blackburn, George L.;Zhou, Jin-Rong
这项工作的目的是确定大豆生物活性成分和他莫昔芬（TAM）在预防雌激素依赖性乳腺癌（BRCA）方面的相互作用。我们初步研究了大豆异黄酮染料木素和TAM对雌激素依赖性MCF-7人BRCA细胞生长和细胞周期进程的影响，以及对体外ER α、pS2和EGFR基因表达的影响。染料木素或TAM单独抑制MCF-7细胞的生长部分是通过G(1)期阻滞，但它们的组合显示出提示的拮抗作用。我们在临床相关的乳腺肿瘤模型中进一步评估了生物活性大豆成分和TAM对MCF-7肿瘤生长抑制的作用。TAM和生物活性大豆成分染料木素和大豆植物化学浓缩物（SPC）可以延缓MCF-7肿瘤的生长。TAM与染料木素或SPC合用，特别是低剂量TAM，对延缓MCF-7肿瘤的生长具有协同作用。生物标志物测定表明，TAM和大豆成分联合使用可能通过诱导肿瘤细胞凋亡和抑制肿瘤细胞增殖的共同作用，协同延缓MCF-7肿瘤的生长。染料木素与TAM联用可通过降低雌激素水平和活性、下调EGFR表达等方式协同延缓乳腺肿瘤的生长。我们的研究结果表明，可能需要进一步的研究来确定TAM和生物活性大豆成分的组合是否可以用于预防和/或治疗雌激素依赖性BRCA。
The objective of this work was to determine the interactive effects between soy bioactive components and tamoxifen (TAM) on prevention of estrogen-dependent breast cancer (BRCA). We initially investigated the effects of soy isoflavone genistein and TAM on the growth and cell cycle progression of estrogen-dependent MCF-7 human BRCA cells, and on the expression of ER alpha, pS2 and EGFR genes in vitro. Genistein or TAM alone inhibited the growth of MCF-7 cells in part via G(1) phase arrest, but their combinations showed suggestive antagonistic effects. We further evaluated the effects of bioactive soy components and TAM on the growth inhibition of MCF-7 tumors in a clinically relevant breast tumor model. TAM and bioactive soy components, genistein and soy phytochemical concentrate (SPC), delayed the growth of MCF-7 tumors. The combination of TAM with genistein or SPC, especially at the lower dose of TAM, had synergistic effects on delaying the growth of MCF-7 tumors. Biomarker determination suggests that the combination of TAM and soy components may synergistically delay the growth of MCF-7 tumors via their combined effects on induction of tumor cell apoptosis and inhibition of tumor cell proliferation. In addition, genistein and TAM combination synergistically delayed the growth of breast tumor via decreased estrogen level and activity, and down-regulation of EGFR expression. The results from our studies suggest that further investigations may be warranted to determine if the combination of TAM and bioactive soy components may be used for prevention and/or treatment of estrogen-dependent BRCA.