Soy phytochemicals prevent orthotopic growth and metastasis of bladder cancer in mice by alterations of cancer cell proliferation and apoptosis and tumor angiogenesis
Soy phytochemicals prevent orthotopic growth and metastasis of bladder cancer in mice by alterations of cancer cell proliferation and apoptosis and tumor angiogenesis
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DOI：
10.1158/0008-5472.can-05-1332
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发表时间：
2006-02-01
期刊：
影响因子：
11.2
通讯作者：
Zhou, JR
中科院分区：
文献类型：
--
作者：
Singh, AV;Franke, AA;Zhou, JR
膳食生物活性成分在预防膀胱癌中的作用在生物学上是合理的，因为大多数物质或代谢物通过尿路排出，因此与膀胱粘膜直接接触。我们首先在体外测定了金雀异黄素对低分化 253J B-V 人膀胱癌细胞的抗生长活性。金雀异黄素通过 G2-M 阻滞、下调核因子 kappa B (NF-kappa B) 和诱导细胞凋亡，以时间和剂量依赖性方式抑制细胞生长。我们还评估了染料木黄酮（染料木黄酮的天然形式）和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 肿瘤生长和转移的影响。用染料木苷和 SPC 治疗的小鼠最终肿瘤重量分别减少了 56% (P < 0.05) 和 52% (P < 0.05)，这与体内诱导肿瘤细胞凋亡和抑制肿瘤血管生成有关。此外，SPC 治疗（而非染料木苷治疗）显着抑制了 95% 的肺转移（P < 0.01），与肿瘤组织中 NF-κ B 表达的显着下调和循环胰岛素样生长因子-I 水平的降低相关，表明 SPC 可能含有其他具有抗转移活性的生物活性成分。我们的研究结果表明，需要进一步的临床研究来应用大豆植物化学物质（例如 SPC）作为膀胱癌进展的有效预防方案。该原位人类膀胱肿瘤模型还提供了临床相关的实验工具，用于评估其他饮食成分对膀胱肿瘤生长和转移的潜在预防活性。
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 G2-M arrest, down-regulation of nuclear factor kappa B (NF-kappa B), 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-kappa B 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.