Inorganic selenium retards progression of experimental hormone refractory prostate cancer
Inorganic selenium retards progression of experimental hormone refractory prostate cancer
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DOI：
10.1097/01.ju.0000092859.16817.8e
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发表时间：
2004-02-01
影响因子：
6.6
通讯作者：
Costello, AJ
中科院分区：
文献类型：
--
作者：
Corcoran, NM;Najdovska, M;Costello, AJ
目的：激素难治性前列腺癌的发展标志着疾病终末期的开始。尽管使用传统的化疗药物以及许多新的代理人的预期寿命没有显着增加超过姑息治疗。硒是一种微量营养素，被纳入一些必需的酶，最低摄入量是维持健康所必需的。在过去的几年里，病例对照和有限的随机对照数据积累的证据表明，超营养剂量的硒可以抑制前列腺癌的进展。虽然许多注意力集中在其作为化学预防剂的用途上，但其作为特异性治疗的用途受到限制。我们假设在实验模型中膳食补充硒会抑制激素难治性前列腺癌的进展。材料和方法：我们在6周龄雄性裸鼠的前列腺中建立了原位PC3肿瘤，并给它们喂食基线硒充足的饮食（0.07 ppm），补充摄入不同形式的硒（硒酸钠、硒代蛋氨酸、甲基硒代半胱氨酸和硒化酵母）（0.3和3 ppm）。结果：无机硒硒酸钠显著延缓了原发性前列腺肿瘤的生长和腹膜后淋巴结转移的发展，这与血管生成的减少有关。高剂量无机硒的膳食补充剂抑制激素难治性前列腺癌的进展，这至少部分是由于血管生成减少。
Purpose: The development of hormone refractory prostate cancer marks the onset of the terminal phase of the disease. Despite the use of traditional chemotherapeutic drugs as well as many novel agents life expectancy is not significantly increased beyond palliative care alone. Selenium is a micronutrient that is incorporated into a number of essential enzymes and a minimum intake is necessary for the maintenance of health. In the last few years evidence has accumulated from case-control and limited randomized control data that supranutritional doses of selenium could inhibit the progression of prostate cancer. While much attention has focused on its use as a chemopreventive agent, its use as specific therapy has been limited. We hypothesized that dietary supplementation of selenium would inhibit the progression of hormone refractory prostate cancer in an experimental model.Materials and Methods: We established orthotopic PC3 tumors in the prostates of 6-week-old male nude mice and fed them a baseline selenium replete diet (0.07 ppm), supplementing intake with different forms of selenium (sodium selenate, selenomethionine, methylselenocysteine and selenized yeast) at 2 different concentrations (0.3 and 3 ppm) in drinking water.Results: Inorganic selenium (sodium selenate) significantly retarded the growth of primary prostatic tumors and the development of retroperitoneal lymph node metastases, which was associated with a decrease in angiogenesis.Conclusions: High dose dietary supplementation of inorganic selenium inhibits the progression of hormone refractory prostate cancer, which is due at least in part to a decrease in angiogenesis.