Green Tea Polyphenol Induces Changes in Cancer-Related Factors in an Animal Model of Bladder Cancer.
Green Tea Polyphenol Induces Changes in Cancer-Related Factors in an Animal Model of Bladder Cancer.
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DOI：
10.1371/journal.pone.0171091
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Sakai H
中科院分区：
文献类型：
--
作者：
Matsuo T;Miyata Y;Asai A;Sagara Y;Furusato B;Fukuoka J;Sakai H
绿色茶多酚（GTP）抑制包括膀胱癌在内的多种恶性肿瘤的致癌作用和侵袭性。然而，这些影响的机制基础还没有得到很好的理解。本研究使用化学诱导膀胱癌的小鼠模型对此进行了研究。用0.05%N-丁基-N-（4-羟丁基）亚硝胺（BBN）溶液处理C3 H/He小鼠（8周龄; n = 46）14-24周。BBN + GTP组（n = 47）小鼠也在相同时间段内用0.5%GTP溶液处理。肿瘤细胞增殖和微血管密度沿着人抗原（Hu）R、血管内皮生长因子（VEGF）-A、环氧合酶（考克斯）-2和血红素氧合酶（HO）-1表达的免疫组织化学分析。BBN组在14周和24周时癌细胞胞质HuR表达高于对照组，并与肌肉中肿瘤细胞浸润增加相关。然而，在BBN + GTP组中未观察到这些作用。GTP摄入和胞浆HuR表达的多变量分析显示，GTP与考克斯-2和HO-1表达独立相关，而胞浆HuR表达与考克斯-2和VEGF-A水平相关。考克斯-2和HO-1的表达与细胞增殖有关，VEGF-A和HO-1的表达与血管生成有关。核HuR表达与任何参数，如癌变，肌肉浸润和GTP摄入量无关。这些结果表明，在膀胱癌的动物模型中，GTP摄入可以抑制肿瘤进展和恶性行为。我们还推测，GTP直接和间接抑制肿瘤细胞增殖和血管生成通过HuR相关的途径在膀胱癌。
Green tea polyphenol (GTP) suppresses carcinogenesis and aggressiveness in many types of malignancies including bladder cancer. However, the mechanistic basis of these effects is not well understood. This was investigated in the present study using a mouse model of chemically induced bladder cancer. C3H/He mice (8 weeks old; n = 46) were treated with 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) solution for 14–24 weeks. Mice in the BBN + GTP group (n = 47) were also treated with 0.5% GTP solution over the same period. Tumor cell proliferation and microvessel density were evaluated along with immunohistochemical analysis of human antigen (Hu)R, vascular endothelial growth factor (VEGF)-A, cyclooxygenase (COX)-2, and hemeoxygenase (HO)-1 expression. Cytoplasmic HuR expression in cancer cells was higher at 14 and 24 weeks in the BBN than in the control group and was associated with increased invasion of tumor cells in muscle. However, these effects were not observed in the BBN + GTP group. A multivariate analysis of GTP intake and cytoplasmic HuR expression revealed that GTP was independently associated with COX-2 and HO-1 expression, while cytoplasmic HuR expression was associated with COX-2 and VEGF-A levels. Expression of COX-2 and HO-1 was associated with cell proliferation and that of VEGF-A and HO-1 was associated with angiogenesis. Nuclear HuR expression was not associated with any parameters such as carcinogenesis, muscle invasion, and GTP intake. These results indicate that GTP intake can suppress tumor progression and malignant behavior in an animal model of bladder cancer. We also speculate that GTP directly and indirectly suppresses tumor cell proliferation and angiogenesis via HuR-related pathways in bladder cancer.