Leong Hoyee, Mathur Priya S, Greene Geoffrey L
The Ben May Department for Cancer Research, The University of Chicago, GCIS W330, 929 East 57th Street, Chicago, IL 60637, USA.
Breast Cancer Res Treat. 2008 Feb;107(3):359-69. doi: 10.1007/s10549-007-9568-x. Epub 2007 May 5.
Previous studies show inhibitory effects of green tea in chemically induced mammary tumors or human tumor explants, but not in spontaneous tumor models that are more representative of human breast cancer. The C3(1)/SV40 mouse model is particularly suited for breast cancer prevention studies because it produces spontaneous ductal adenocarcinomas and a predictable time course for mammary tumorigenesis through a multistage progression similar to that occurring in humans. We therefore used this model to test the chemoprotective effects of green tea. Administration of 0.5% Polyphenon E (Poly E) (a standardized preparation of green tea extract) in drinking water delayed tumor onset and suppressed tumor growth by 40%, compared to tap water-fed animals, with no adverse side effects. Histological analysis of mammary glands showed that green tea slowed the progression of ductal lesions to advanced mammary intraepithelial neoplasias and suppressed tumor invasiveness. Green tea inhibited the proliferation of ductal epithelial cells and tumors and, overall, disrupted post-pubertal ductal growth. Immunohistochemical analyses also demonstrated that green tea inhibited angiogenesis through a decrease in both ductal epithelial and stromal VEGF expression and a decrease in intratumoral microvascular density. Our data strongly support the potential use of green tea as a breast cancer chemopreventive agent.
先前的研究表明，绿茶对化学诱导的乳腺肿瘤或人肿瘤外植体有抑制作用，但对更能代表人类乳腺癌的自发肿瘤模型却没有抑制作用。C3(1)/SV40小鼠模型特别适合用于乳腺癌预防研究，因为它会产生自发性导管腺癌，并且通过与人类相似的多阶段进展过程，呈现出可预测的乳腺肿瘤发生时间进程。因此，我们使用该模型来测试绿茶的化学保护作用。与饮用自来水的动物相比，在饮用水中添加0.5%的茶多酚E（Poly E，一种标准化的绿茶提取物制剂）可延迟肿瘤发生，并使肿瘤生长抑制40%，且无不良副作用。对乳腺的组织学分析表明，绿茶减缓了导管病变向晚期乳腺上皮内瘤变的进展，并抑制了肿瘤的侵袭性。绿茶抑制了导管上皮细胞和肿瘤的增殖，总体上破坏了青春期后导管的生长。免疫组织化学分析还表明，绿茶通过降低导管上皮和基质中的血管内皮生长因子（VEGF）表达以及肿瘤内微血管密度，抑制了血管生成。我们的数据有力地支持了绿茶作为乳腺癌化学预防剂的潜在用途。
