15-lipoxygenase-1 has anti-tumorigenic effects in colorectal cancer

15-lipoxygenase-1 has anti-tumorigenic effects in colorectal cancer
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DOI:
10.1016/j.plefa.2003.06.001
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发表时间:
2004-01-01
影响因子:
3
通讯作者:
Eling, TE
Eling, TE
中科院分区:
医学4区
文献类型:
--
作者:
Nixon, JB;Kim, KS;Eling, TE

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应用免疫组织化学方法检测15-脂氧合酶-1(15-LO-1)在大肠癌及癌旁正常组织中的定位。在正常组织中,15-LO-1强烈定位于粘膜上皮中。相反,在肿瘤组织中,15-LO-1的染色分散在整个组织中,在肿瘤上皮中较弱,在基质炎性细胞中较强。加入50 μ M的13(S)-羟基二十碳四烯酸(HODE)导致72小时后细胞增殖降低,但与载体处理的Caco-2细胞相比,较低浓度(5或10 μ M)没有影响。此外,13(S)-HODE对Caco-2细胞的凋亡或分化没有影响。用50 μ M 13(S)-HODE处理的Caco-2细胞的RNA的微阵列分析揭示了17个基因的变化。HCT-116结肠直肠细胞用15-LO-1稳定转染。在无胸腺裸鼠中,源自15-LO-1 HCT-116细胞的可移植肿瘤小于源自载体HCT-116细胞的肿瘤。这些数据表明,13(S)-HODE诱导基因表达的变化,并具有抗肿瘤作用。爱思唯尔有限公司出版
The localization of 15-lipoxygenase-1 (15-LO-1) in human colorectal carcinoma and normal adjacent tissue was examined using immunohistochemistry. In normal tissues, 15-LO-1 was strongly localized in the mucosal epithelium. Conversely, in tumor tissues, staining for 15-LO-1 was dispersed throughout the tissue, weak in neoplastic epithelium, and strong in stromal inflammatory cells. The addition of 50 muM 13(S)-hydroxyeicosatetraenoic acid (HODE), resulted in decreased cell proliferation after 72 h, but lower concentrations (5 or 10 muM) had no effect compared to vehicle treated Caco-2 cells. In addition, 13(S)-HODE had no effect on apoptosis or differentiation of the Caco-2 cells. Microarray analyses of RNA from Caco-2 cells treated with 50 muM 13(S)-HODE revealed changes in 17 genes. HCT-116 colorectal cells were stably transfected with 15-LO-1. In athymic nude mice, transplantable tumors derived from 15-LO-1 HCT-116 cells were smaller than tumors derived from vector HCT-116 cells. These data demonstrate that 13(S)-HODE induces changes in gene expression and has anti-tumorigenic effects. Published by Elsevier Ltd.