Methaneseleninic acid and γ-Tocopherol combination inhibits prostate tumor growth in Vivo in a xenograft mouse model.
Methaneseleninic acid and γ-Tocopherol combination inhibits prostate tumor growth in Vivo in a xenograft mouse model.
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DOI：
10.18632/oncotarget.1979
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发表时间：
2014-06-15
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影响因子：
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通讯作者：
Ahmad N
中科院分区：
文献类型：
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作者：
Singh CK;Ndiaye MA;Siddiqui IA;Nihal M;Havighurst T;Kim K;Zhong W;Mukhtar H;Ahmad N
研究表明，维生素E和硒对前列腺癌（PCa）具有抗增殖作用。然而，硒和维生素E癌症预防试验（SELECT）的结果表明，维生素E（α-生育酚乙酸酯; 400 mg）和/或硒（L-硒代蛋氨酸; 200 μg）对人体PCa无效。可以肯定的是，维生素E/硒的选定剂量/制剂在SELECT中不是最佳的。因此，需要额外的研究来确定这些药物的适当制剂/给药方案。在此，我们研究了甲硒酸（MSA; 41 μg/kg）和/或γ-生育酚（γT; 20.8 mg/kg或41.7 mg/kg）在植入22 R ν1肿瘤的Nu/J小鼠中的作用。MSA（41 μg/kg）和γT（20.8 mg/kg）联合给药在产生抗增殖反应方面最为一致;导致i）肿瘤体积/重量、ii）血清PSA和iii）Ki-67免疫染色显著降低。此外，我们观察到i）促凋亡Bax的上调和促存活Bcl 2的下调，和ii）促凋亡Bad的增加。此外，该组合导致载脂蛋白E、硒蛋白P和Nrf 2以有利于抗增殖反应的方式调节。总体而言，我们的研究表明，MSA和γT的组合，在较低的剂量方案，可能是有用的PCa管理。
Studies have shown that vitamin E and selenium possess antiproliferative effects against prostate cancer (PCa). However, results from the Selenium and Vitamin E Cancer Prevention Trial (SELECT) suggest that vitamin E (α-tocopheryl acetate; 400 mg) and/or selenium (L-selenomethionine; 200 μg) were ineffective against PCa in humans. It is arguable that the selected dose/formulation of vitamin E/selenium were not optimal in SELECT. Thus, additional studies are needed to define the appropriate formulations/dose regimens of these agents. Here, we investigated the effect of methaneseleninic acid (MSA; 41 μg/kg) and/or γ-tocopherol (γT; 20.8 mg/kg or 41.7 mg/kg) in Nu/J mice implanted with 22Rν1 tumors. MSA (41 μg/kg) and γT (20.8 mg/kg) combination was most consistent in imparting anti-proliferative response; resulting in a significant decrease in i) tumor volume/weight, ii) serum PSA, and iii) Ki-67 immunostaining. Further, we observed i) an upregulation of pro-apoptosis Bax and a down-regulation of the pro-survival Bcl2, and ii) an increase in pro-apoptosis Bad. Furthermore, the combination resulted in a modulation of apolipoprotein E, selenoprotein P and Nrf2 in a fashion that favors antiproliferative responses. Overall, our study suggested that a combination of MSA and γT, at lower dose regimen, could be useful in PCa management.