15-脂氧合酶-1在结直肠癌中具有抗肿瘤作用。

15-Lipoxygenase-1 has anti-tumorigenic effects in colorectal cancer.

作者信息

Nixon Jennifer B, Kim Kyung Su, Lamb Patricia W, Bottone Frank G, Eling Thomas E

机构信息

Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, PO Box 12233, Research Triangle Park, NC 27709, USA.

出版信息

Prostaglandins Leukot Essent Fatty Acids. 2004 Jan;70(1):7-15. doi: 10.1016/j.plefa.2003.06.001.

DOI:10.1016/j.plefa.2003.06.001

PMID:14643174

Abstract

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 microM 13(S)-hydroxyeicosatetraenoic acid (HODE), resulted in decreased cell proliferation after 72 h, but lower concentrations (5 or 10 microM) 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 5 microM 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.

摘要

采用免疫组织化学方法检测了15-脂氧合酶-1（15-LO-1）在人大肠癌组织及癌旁正常组织中的定位。在正常组织中，15-LO-1主要定位于黏膜上皮。相反，在肿瘤组织中，15-LO-1染色分散于整个组织，在肿瘤上皮中较弱，而在基质炎性细胞中较强。加入50μM 13(S)-羟基二十碳四烯酸（HODE）后，72小时后细胞增殖减少，但与载体处理的Caco-2细胞相比，较低浓度（5或10μM）无作用。此外，13(S)-HODE对Caco-2细胞的凋亡或分化无影响。对用5μM 13(S)-HODE处理的Caco-2细胞的RNA进行微阵列分析，发现17个基因发生了变化。用15-LO-1稳定转染HCT-116大肠癌细胞。在无胸腺裸鼠中，源自15-LO-1 HCT-116细胞的可移植肿瘤比源自载体HCT-116细胞的肿瘤小。这些数据表明，13(S)-HODE可诱导基因表达变化并具有抗肿瘤作用。