Methyl-selenium compounds inhibit prostate carcinogenesis in the transgenic adenocarcinoma of mouse prostate model with survival benefit.
Methyl-selenium compounds inhibit prostate carcinogenesis in the transgenic adenocarcinoma of mouse prostate model with survival benefit.
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DOI：
10.1158/1940-6207.capr-08-0173
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发表时间：
2009-05
期刊：
影响因子：
--
通讯作者：
Lü J
中科院分区：
文献类型：
--
作者：
Wang L;Bonorden MJ;Li GX;Lee HJ;Hu H;Zhang Y;Liao JD;Cleary MP;Lü J
通过第二代硒化合物（涉及硒代蛋氨酸）对前列腺癌进行化学预防，有望从根本上解决该疾病。在这里，我们使用转基因小鼠前列腺腺癌 (TRAMP) 模型来建立甲基硒酸 (MSeA) 和甲基硒代半胱氨酸 (MSeC) 抗前列腺癌的功效并表征潜在机制。八周大的雄性 TRAMP 小鼠（C57B/6 背景）每天口服剂量为 3 mg Se/kg 体重的水、MSeA 或 MSeC，并在 18 或 26 周龄时处以安乐死。到 18 周龄时，MSeA 和 MSeC 治疗组的泌尿生殖 (GU) 道和前列腺背侧 (DLP) 重量低于对照组 (p<0.01)。第 26 周时，每 10 只对照小鼠中有 4 只的 GU 重量超过 2 克，而每个硒组中只有十分之一的小鼠的 GU 重量超过 2 克。与对照小鼠相比，Se 治疗小鼠的 DLP 中 T 抗原表达没有明显变化，并且血清 IGF-1 降低，其功效还包括延迟病变进展、增加细胞凋亡和减少增殖。在另一项实验中，从 10 周或 16 周龄开始给予 TRAMP 小鼠 MSeA，可将其存活率提高至 50 周龄，并延迟因突触素阳性神经内分泌癌、突触素阴性前列腺病变和精囊肥大而导致的死亡。与对照小鼠相比，从 10 周开始接受 MSeA 的野生型小鼠没有表现出体重、GU 重量下降或血清 ALT 增加。因此，这些硒化合物可能有效抑制这种PCa致癌模型。
Chemoprevention of prostate cancer by second-generation selenium compounds in reference to selenomethionine holds strong promise to deal with the disease at the root. Here we used the transgenic adenocarcinoma mouse prostate (TRAMP) model to establish the efficacy of methylseleninic acid (MSeA) and methylselenocysteine (MSeC) against prostate carcinogenesis and to characterize potential mechanisms. Eight-week-old male TRAMP mice (C57B/6 background) were given a daily oral dose of water, MSeA or MSeC at 3 mg Se/kg body weight and were euthanized at either 18 or 26 weeks of age. By 18 weeks of age, the genito-urinary (GU) tract and dorsal-lateral prostate (DLP) weights for the MSeA and MSeC-treated groups were lower than for the control (p<0.01). At 26 weeks, 4 out of 10 control mice had GU weight over 2 g, only 1 out of 10 in each of the Se groups did. The efficacy was accompanied by delayed lesion progression, increased apoptosis and decreased proliferation without appreciable changes of T-antigen expression in the DLP of Se-treated mice and decreased serum IGF-1 when compared to control mice. In another experiment, giving MSeA to TRAMP mice from 10-weeks or 16-weeks of age increased their survival to 50 weeks of age, and delayed the death due to synaptophysin-positive neuroendocrine carcinomas and synaptophysin-negative prostate lesions and seminal vesicle hypertrophy. Wild-type mice receiving MSeA from 10 weeks did not exhibit decreased body weight, GU weight or increased serum ALT than the control mice. Therefore, these selenium compounds may effectively inhibit this model of PCa carcinogenesis.