Combination of calcitriol and dietary soy exhibits enhanced anticancer activity and increased hypercalcemic toxicity in a mouse xenograft model of prostate cancer.
Combination of calcitriol and dietary soy exhibits enhanced anticancer activity and increased hypercalcemic toxicity in a mouse xenograft model of prostate cancer.
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DOI：
10.1002/pros.22516
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发表时间：
2012-11
期刊：
影响因子：
2.8
通讯作者：
Feldman, David
中科院分区：
文献类型：
--
作者：
Wang, Jennifer Y.;Swami, Srilatha;Krishnan, Aruna V.;Feldman, David
近年来，维生素D和大豆在前列腺癌（PCa）预防/治疗中的潜在作用引起了人们的广泛关注。在这项研究中，我们评估了骨化三醇、维生素D的活性形式、膳食大豆及其组合在PCa小鼠模型中的抗癌活性。携带PC-3人PCa异种移植物的胸腺雄性裸鼠接受含有10千卡或20千卡大豆、骨化三醇注射剂或大豆和骨化三醇组合的饮食。检测肿瘤生长、血清1,25(OH)2D和钙水平的变化以及肿瘤基因表达的调节。联合治疗对肿瘤生长的抑制作用明显大于单独使用任何一种药物。大豆饮食单独引起血清125 (OH)2D的适度升高，而骨化三醇-大豆组合导致血清125 (OH)2D大幅升高，高钙血症，在某些情况下导致致命毒性。这些组合增强了骨化三醇调节靶基因表达的活性，包括抗增殖（p21, IGFBP-3）和促凋亡（Bax）基因的上调，抗凋亡（Bcl-2）和细胞周期促进（cyclin D1）基因的抑制增加，以及前列腺素（PG）合成和信号传导（COX-2, 15-PGDH， PG受体）的抑制。血清钙的升高伴随着肠道钙吸收基因（TRPV6、钙结合蛋白-9k）的表达升高。大豆增加内源性和给药骨化三醇的生物利用度，从而增强其抗癌作用和高钙血症的风险。由于这两种药物都很容易作为膳食补充剂获得，当考虑在PCa治疗中联合使用维生素D和大豆时，高钙中毒的潜在增加成为一个重要因素。
The potential role of vitamin D and soy in prostate cancer (PCa) prevention/treatment has gained much attention in recent years. In this study, we evaluated the anticancer activity of calcitriol, the active form of vitamin D, dietary soy, and their combinations in a mouse model of PCa. Athymic male nude mice bearing PC-3 human PCa xenografts received diets containing 10 kcal% or 20 kcal% soy, calcitriol injections, or a combination of dietary soy and calcitriol. Changes in tumor growth, serum levels of 1,25(OH)2D and calcium, and regulation of tumor gene expression were examined. The combination treatments resulted in substantially greater inhibition of tumor growth than either agent alone. Soy diets alone caused a modest elevation in serum 1,25(OH)2D, whereas the calcitriol-soy combinations led to substantially elevated serum 1,25(OH)2D, hypercalcemia, and in some cases lethal toxicity. The combinations enhanced calcitriol activity in regulating target gene expression, including greater up-regulation of anti-proliferative (p21, IGFBP-3) and pro-apoptotic (Bax) genes, increased inhibition of anti-apoptotic (Bcl-2) and cell cycle promoting (cyclin D1) genes, and suppression of prostaglandin (PG) synthesis and signaling (COX-2, 15-PGDH, PG receptors). Increases in serum calcium were accompanied by elevated expression of intestinal calcium absorption genes (TRPV6, calbindin-9k). Soy increases the bioavailability of endogenous and administered calcitriol, thereby enhancing its anticancer effects and risk of hypercalcemia. Since both agents are easily available as dietary supplements, the increased potential for hypercalcemic toxicity becomes an important factor when considering the combined use of vitamin D and soy in PCa therapy.
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影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
维生素D在预防和治疗中的作用。
DOI：
10.1016/j.ecl.2010.02.011
发表时间：
2010-06
影响因子：
4.5
作者：
Krishnan AV;Trump DL;Johnson CS;Feldman D
通讯作者：
Feldman D
影响因子：
4.2
作者：
Kállay, E;Adlercreutz, H;Cross, HS
通讯作者：
Cross, HS
影响因子：
23.4
作者：
Bektic, J;Berger, AP;Klocker, H
通讯作者：
Klocker, H
影响因子：
30.8
作者：
Albertson, DG;Ylstra, B;Pinkel, D
通讯作者：
Pinkel, D