Vitamin D inhibition of prostate adenocarcinoma growth and metastasis in the Dunning rat prostate model system
Vitamin D inhibition of prostate adenocarcinoma growth and metastasis in the Dunning rat prostate model system
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DOI：
10.1016/s0090-4295(97)00408-1
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发表时间：
1997-12-01
期刊：
影响因子：
2.1
通讯作者：
Johnson, CS
中科院分区：
文献类型：
--
作者：
Getzenberg, RH;Light, BW;Johnson, CS
目标。前列腺癌（PCa）相关死亡率的危险因素包括老年、黑人种族和居住在北纬地区。本研究的目的是研究1,25-二羟基胆钙化醇（1,25- d -3）和低高钙类似物对Dunning大鼠前列腺癌模型的体内外作用。为了评估1,25- d -3对体外前列腺癌的影响，我们使用了高度转移的Mat-lylu （MLL）和中度转移的R3327-AT-2 (AT-2) Dunning前列腺细胞系，并研究了对生长、克隆性、分化和细胞周期的影响。体内分析包括检查这些化合物对肿瘤生长和转移的影响。通过3天的MTT和7天的克隆实验，1,25- d -3对MLL和AT-2的生长抑制作用显示出50%的抑制浓度（IC50）约为20 μ M。细胞周期分析显示，MLL细胞（10 μ m1,25 - d -3处理48小时）的G(0)/G(1)期细胞比对照细胞多25%。为了研究1,25-D-3和低钙维生素D类似物Ro25-6760（或6760）对MLL前列腺癌生长和转移的体内影响，在开始用1,25-D-3 （1 μ g）或6760（1或5 μ g）治疗的同一天，将肿瘤（5 × 10(5)个细胞）皮下植入哥本哈根大鼠的侧腹；大鼠每周接受三次治疗。3周后，1,25- d -3和6760 （5 μ g剂量）抑制肿瘤体积，减少肺转移灶的数量和大小。这些临床前研究证明了1,25- d -3和6760对前列腺癌具有深远的体外或体内抗增殖和分化作用，并提示这些药物可能对晚期前列腺癌的治疗有潜在的有益作用。(C) 1997, Elsevier Science Inc.；版权所有。
Objectives. Risk factors for prostate cancer (PCa)-related mortality include old age, black race, and residence in northern latitudes. The objectives of this study are to examine the in vitro and in vivo effects of 1,25-dihydroxycholecalciferol (1,25-D-3) and less-hypercalcemic analogues on the Dunning rat prostate adenocarcinoma model.Methods. To evaluate the effect of 1,25-D-3 on PCa in vitro, we used the highly metastatic Mat-lylu (MLL) and moderately metastatic R3327-AT-2 (AT-2) Dunning prostate cell lines, and examined effects on growth, clonogenicity, differentiation, and cell cycle. in vivo analysis included examination of the effects of these compounds on tumor growth and metastasis.Results. Using both the 3-day MTT and 7-day clonogenic assay, 1,25-D-3 demonstrated a growth inhibitory effect with a concentration for 50% inhibition (IC50) of approximately 20 mu M for both MLL and AT-2. Cell cycle analysis of treated MLL cells (10 mu M 1,25-D-3 for 48 hours) had 25% more cells in the G(0)/G(1) phase than did control cells. To examine the in vivo effect of 1,25-D-3 and the less hypercalcemic Vitamin D analogue, Ro25-6760 (or 6760), on MLL PCa growth and metastasis, tumors (5 x 10(5) cells) were implanted subcutaneously into the flank of Copenhagen rats on the same day that treatment was initiated with 1,25-D-3 (1 mu g) or 6760 (1 or 5 mu g); rats received treatment three times a week. After 3 weeks, 1,25-D-3 and 6760 (5 mu g dosing) resulted in an inhibition of tumor volume and a reduction in the number and size of lung metastases.Conclusions. These preclinical studies demonstrate the profound in vitro, or in vivo, or both antiproliferative and differentiating effects of 1,25-D-3 and 6760 on PCa and suggest that these drugs may have potential beneficial effects in the treatment of advanced PCa. (C) 1997, Elsevier Science Inc. All rights reserved.