Department of Pathology, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA.
Department of Urology, University of Minnesota Medical School, Minneapolis, MN, USA.
Nutr Cancer. 2022;74(10):3761-3768. doi: 10.1080/01635581.2022.2093387. Epub 2022 Jun 28.
Selenomethionine (SeMet) did not prevent prostate cancer in the SELECT trial and in two hormone-driven rat models. However, we have shown that daily oral bolus administration of next-generation selenium forms, methylseleninic acid (MSeA) and Se-methylselenocysteine (MSeC) at 3 mg Se/kg body weight, inhibits prostate carcinogenesis in the TRAMP and -deficient mouse models and In Vivo growth of human prostate cancer cells. Here, we determined whether these Se forms prevent prostate cancer in a chemically induced-androgen promoted carcinogenesis rat model in which SeMet was not preventive. WU rats were treated with methylnitrosourea, and one week later, slow-release testosterone implants when they were randomized to groups fed AIN-93M diet supplemented with 3 ppm selenium as MSeA or MSeC or control diet. Mean survival, tumor incidence in all accessory sex glands combined (dorsolateral and anterior prostate plus seminal vesicle) and the incidence of tumors confined to dorsolateral and/or anterior prostate were not statistically significantly different among the groups. Thus, MSeA and MSeC feeding was not preventive in this model. The contrast with the inhibitory effects of MSeA and MSeC in mouse models may be due to differences in carcinogenic mechanisms, selenium dosage, delivery mode, and pharmacokinetics or fundamental rat-mouse differences in selenium metabolism.
硒代蛋氨酸（SeMet）在 SELECT 试验和两种激素驱动的大鼠模型中均不能预防前列腺癌。然而，我们已经表明，每天口服给予新一代硒形式，即亚硒酸（MSeA）和硒代蛋氨酸（MSeC），剂量为 3mg/kg 体重，可以抑制 TRAMP 和 -缺陷小鼠模型中的前列腺癌发生，以及人前列腺癌细胞的体内生长。在这里，我们确定这些硒形式是否可以预防化学诱导-雄激素促进的致癌作用大鼠模型中的前列腺癌，在该模型中，硒代蛋氨酸没有预防作用。WU 大鼠用亚硝脲处理，一周后，当它们被随机分为 AIN-93M 饮食补充 3ppm 硒作为 MSeA 或 MSeC 或对照饮食的组时，给予缓释睾酮植入物。各组之间的平均存活时间、所有附属性器官（背外侧和前前列腺加精囊）的肿瘤发生率以及局限于背外侧和/或前前列腺的肿瘤发生率均无统计学差异。因此，在该模型中，MSeA 和 MSeC 的喂养没有预防作用。与 MSeA 和 MSeC 在小鼠模型中的抑制作用形成对比的可能是由于致癌机制、硒剂量、给药方式、药代动力学或硒代谢的基本大鼠-小鼠差异所致。
