Mixed Tocotrienols Inhibit Prostate Carcinogenesis in TRAMP Mice
Mixed Tocotrienols Inhibit Prostate Carcinogenesis in TRAMP Mice
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DOI：
10.1080/01635581003605896
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发表时间：
2010-01-01
影响因子：
2.9
通讯作者：
Kong, Ah-Ng
中科院分区：
文献类型：
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作者：
Barve, Avantika;Khor, Tin Oo;Kong, Ah-Ng
生育三烯醇的生物活性受到越来越多的关注。在此，我们报告了混合生育三烯醇饮食对转基因小鼠前列腺癌(TRAMP)小鼠模型前列腺癌形成的疗效。雄性流浪鼠，8周龄，饲喂含0.1%、0.3%或1%混合生育三烯醇的AIN-76A饲料至24周。同样，一组由雄性流浪鼠组成的阳性对照组和一组由野生型非转基因小鼠组成的阴性对照组被喂以常规的AIN-76A饮食，直到24周。我们的结果显示，混合生育三烯醇喂养组的肿瘤形成发生率较低，同时泌尿生殖器官的平均湿重显着降低。此外，与阳性对照相比，混合生育三烯醇显著降低了高级别肿瘤病变的水平。这种高级别肿瘤病变水平的下降被发现与促凋亡蛋白BAD(Bcl2细胞死亡拮抗剂)和裂解的caspase-3以及细胞周期调节蛋白Cyclin依赖的激酶抑制物p21和p27的表达增加有关。相反，在混合生育三烯醇组，细胞周期蛋白A和E的表达减少。综上所述，我们的结果表明，通过调节细胞周期调节蛋白和增加促凋亡蛋白的表达，混合生育三烯醇抑制了TRAMP小鼠的前列腺癌的发生。
The biological activities of tocotrienols are receiving increasing attention. Herein, we report the efficacy of a mixed-tocotrienol diet against prostate tumorigenesis in the transgenic adenocarcinoma mouse prostate (TRAMP) mouse model. Male TRAMP mice, 8 wk old, were fed 0.1%, 0.3%, or 1% mixed tocotrienols in AIN-76A diet up to 24 wk old. Likewise, a positive control group consisting of male TRAMP mice and a negative control group consisting of wild-type nontransgenic mice were fed regular AIN-76A diet up to 24 wk old. Our results show that mixed-tocotrienol-fed groups had a lower incidence of tumor formation along with a significant reduction in the average wet weight of genitourinary apparatus. Furthermore, mixed tocotrienols significantly reduced the levels of high-grade neoplastic lesions as compared to the positive controls. This decrease in levels of high-grade neoplastic lesions was found to be associated with increased expression of proapoptotic proteins BAD (Bcl2 antagonist of cell death) and cleaved caspase-3 and cell cycle regulatory proteins cyclin dependent kinase inhibitors p21 and p27. In contrast, the expression of cyclins A and E were found to be decreased in mixed-tocotrienol groups. Taken together, our results show that by modulating cell cycle regulatory proteins and increasing expression of proapoptotic proteins, mixed tocotrienols suppress prostate tumorigenesis in the TRAMP mice.