Cancer Research, 2006, 66(3):1851.

Soy Phytochemicals Prevent Orthotopic Growth and Metastasis of Bladder Cancer in Mice by Alterations of Cancer Cell Proliferation and Apoptosis and Tumor Angiogenesis

Ajita V. Singh, George L. Blackburn, Jin-Rong Zhou, et al

Nutrition/Metabolism Laboratory, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, assachusetts ；Cancer Research Center of Hawaii, University of Hawaii, Honolulu, Hawaii

A role of dietary bioactive components in bladder cancer prevention is biologically plausible because most substances or metabolites are excreted through the urinary tract and are consequently in direct contact with the mucosa of the bladder. We first determined antigrowth activity of genistein against poorly differentiated 253J B-V human bladder cancer cells in vitro. Genistein inhibited the cell growth in a time- and dose-dependent manner via G(2)-M arrest, down-regulation of nuclear factor kappaB (NF-kappaB), and induction of apoptosis. We also evaluated both genistin, which is a natural form of genistein, and the isoflavone-rich soy phytochemical concentrate (SPC) on the growth and metastasis of 253J B-V tumors in an orthotopic tumor model. Mice treated with genistin and SPC had reduced final tumor weights by 56% (P < 0.05) and 52% (P < 0.05), respectively, associated with induction of tumor cell apoptosis and inhibition of tumor angiogenesis in vivo. In addition, SPC treatment, but not genistin treatment, significantly inhibited lung metastases by 95% (P < 0.01) associated with significant down-regulation of NF-kappaB expression in tumor tissues and reduction of circulating insulin-like growth factor-I levels, suggesting that SPC may contain other bioactive ingredients that have antimetastatic activity. The results from our studies suggest that further clinical investigation should be warranted to apply soy phytochemicals, such as SPC, as a potent prevention regimen for bladder cancer progression. This orthotopic human bladder tumor model also provides a clinically relevant experimental tool for assessing potential preventive activity of other dietary components against bladder tumor growth and metastasis.

美国《癌症研究》，2006年

大豆植物化学物质通过改变癌细胞增殖和细胞凋亡和肿瘤血管生成来预防小鼠膀胱癌的原位生长和转移

艾吉塔 V 辛格，乔治 L 布莱克本，周锦荣，等

营养/代谢实验室，贝斯以色列女执事医学中心外科，哈佛医学院，波士顿，美国;夏威夷夏威夷癌症研究中心，夏威夷檀香山

饮食生物活性成分在膀胱癌预防中的作用在生物学上似乎是合理的，因为大多数物质或代谢物通过尿道排出，因此与膀胱粘膜直接接触。我们首先确定了染料木素对体外低分化253J B-V人膀胱癌细胞的抗生长活性。染料木黄酮通过G（2）-M阻滞，核因子κB（NF-kappaB）下调和细胞凋亡诱导，以时间和剂量依赖的方式抑制细胞生长。我们还评估了染料木素（genistin），它是一种天然形式的染料木素，富含异黄酮的大豆植物化学浓缩物（SPC）对原位肿瘤模型中253J B-V肿瘤的生长和转移进行了评估。用染料木苷和SPC处理的小鼠分别与肿瘤细胞凋亡诱导和体内肿瘤血管发生的抑制相关联，最终肿瘤重量分别降低了56％（P <0.05）和52％（P <0.05）。此外，SPC治疗，但不是染料木苷治疗，显着抑制肺转移95％（P <0.01）与肿瘤组织中NF-κB表达的显着下调和循环胰岛素样生长因子-1水平的降低相关，表明SPC可能含有具有抗转移活性的其他生物活性成分。我们研究的结果表明，进一步的临床调查应该是应用大豆植物化学物质，如SPC，作为膀胱癌进展的有效预防方案。这种原位人膀胱肿瘤模型还提供了临床相关的实验工具，用于评估其他饮食组分对膀胱肿瘤生长和转移的潜在预防活性。