Growth inhibition of prostate cancer xenografts by halofuginone
Growth inhibition of prostate cancer xenografts by halofuginone
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DOI：
10.1002/pros.10059
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发表时间：
2002-05-01
期刊：
影响因子：
2.8
通讯作者：
Pines, M
中科院分区：
文献类型：
--
作者：
Gavish, Z;Pinthus, FH;Pines, M
背景常山酮是一种I型胶原合成抑制剂，是一种抗血管生成剂。在这里，我们评估了常山酮抑制前列腺癌（PC）异种移植物的疗效，代表了疾病的各种表型。使用雄激素依赖性（CWR 22）、雄激素非依赖性（PC 3）和神经内分泌（WISH-PC 2）PC异种移植物。口服或腹腔注射常山酮。评估肿瘤大小、胶原α 1（l）基因表达（原位杂交）、胶原含量（天狼星红染色）、血管生成（因子VIII抗体免疫组化）和凋亡/坏死（DNA片段化）。常山酮抑制所有皮下移植的异种移植物和原位移植时的WISH-PC 2的生长。该效应具有剂量依赖性（WISH-PC 2），并伴有血浆PSA水平降低（CWR 22）。在所有异种移植物中，常山酮抑制胶原α 1（1）基因表达，减少胶原含量和内皮细胞数量，导致细胞凋亡/坏死增加。口服常山酮减缓了PC异种移植物的进展，代表了广泛的表型。常山酮可能成为预防PC的新方法。(C)2002 Wiley-Liss，Inc.
BACKGROUND. Halofuginone, an inhibitor of collagen type I synthesis, is an anti-angiogenic agent. Here we evaluated the efficacy of halofuginone to inhibit prostate cancer (PC) xenografts representing various phenotypes of the disease.METHODS. An androgen-dependent (CWR22), an androgen-independent (PC3), and a neuroendocrine (WISH-PC2) PC xenograft were used. Halofuginone was given orally or injected intraperitoneally. Tumor size, collagen alpha1(l) gene expression (in situ hybridization), collagen content (sirius red staining), angiogenesis (immunohistochemistry with factor VIII antibodies), and apoptosis/necrosis (DNA fragmentation) were evaluated.RESULTS. Halofuginone inhibited the growth of all subcutaneously implanted xenografts and of WISH-PC2 when transplanted orthotopically. The effect was dose-dependent (WISH-PC2) and accompanied by decrease in plasma PSA levels (CWR22). In all xenografts, halofuginone inhibited collagen alpha1(l) gene expression, reduced collagen content, and endothelial cell number resulting in an increase in apoptosis/necrotsis.CONCLUSIONS. Oral administration of halofuginone slowed the progression of PC xenografts representing a broad range of phenotypes. Halofuginone may become a new modality for PC prevention. (C) 2002 Wiley-Liss, Inc.