生物谷报道:美国西北大学研究人员发现,大豆中含有一种叫三羟基异黄酮的抗氧化剂几乎能完全遏制前列腺癌细胞在老鼠体内扩散。
美国癌症研究协会出版的最新一期《癌症研究》上刊登的一篇文章说,美国西北大学研究人员在老鼠身上进行的实验显示,服用三羟基异黄酮的老鼠前列腺癌细胞转移到肺
部的几率减少了96%。实验中使用的三羟基异黄酮含量也就相当于人从一顿富含豆制品的饮食中摄取的量。
西北大学罗伯特·卢里综合癌症中心的雷蒙德·伯根说:“这些实验结果给了我们新的希望,在阻止前列腺癌细胞扩散方面,三羟基异黄酮或许能产生一定效果。”
研究人员发现,虽然三羟基异黄酮不会使前列腺肿瘤变小,但它几乎能完全阻止前列腺癌细胞转移到肺部。
生物谷推荐原始出处:
(Cancer Research),68, 2024-2032,Minalini Lakshman,Raymond C. Bergan
etary Genistein Inhibits Metastasis of Human Prostate Cancer in Mice
Minalini Lakshman1, Li Xu1, Vijayalakshmi Ananthanarayanan2, Joshua Cooper4, Chris H. Takimoto4, Irene Helenowski2, Jill C. Pelling3 and Raymond C. Bergan1
1 Division of Hematology/Oncology, Department of Medicine, 2 Department of Preventive Medicine, and 3 Department of Pathology, Northwestern University Medical School and Robert H. Lurie Cancer Center of Northwestern University, Chicago, Illinois and 4 Institute for Drug Development, San Antonio, Texas
Requests for reprints: Raymond C. Bergan, Olson 8321, 710 North Fairbanks, Chicago, IL 60611-3008. Phone: 312-908-5284; Fax: 312-503-4744; E-mail: r-bergan@northwestern.edu .
Key Words: chemoprevention • prostate cancer • soy • metastasis • mouse model
Dietary genistein has been linked to lower prostate cancer (PCa) mortality. Metastasis is the ultimate cause of death from PCa. Cell detachment and invasion represent early steps in the metastatic cascade. We had shown that genistein inhibits PCa cell detachment and cell invasion in vitro. Genistein-mediated inhibition of activation of focal adhesion kinase (FAK) and of the p38 mitogen-activated protein kinase (MAPK)–heat shock protein 27 (HSP27) pathway has been shown by us to regulate PCa cell detachment and invasion effects, respectively. To evaluate the antimetastatic potential of genistein, we developed an animal model suited to evaluating antimetastatic drug efficacy. Orthotopically implanted human PC3-M PCa cells formed lung micrometastasis by 4 weeks in >80% of inbred athymic mice. Feeding mice dietary genistein before implantation led to blood concentrations similar to those measured in genistein-consuming men. Genistein decreased metastases by 96%, induced nuclear morphometric changes in PC3-M cells indicative of increased adhesion (i.e., decreased detachment) but did not alter tumor growth. Genistein increased tumor levels of FAK, p38 MAPK, and HSP27 "promotility" proteins. However, the ratio of phosphorylated to total protein trended downward, indicating a failure to increase relative amounts of activated protein. This study describes a murine model of human PCa metastasis well suited for testing antimetastatic drugs. It shows for the first time that dietary concentrations of genistein can inhibit PCa cell metastasis. Increases in promotility proteins support the notion of cellular compensatory responses to antimotility effects induced by therapy. Studies of antimetastatic efficacy in man are warranted and are under way. [Cancer Res 2008;68(6):2024–32]