Department of Biological Sciences, Middle East Technical University, Ankara, Turkey.
Cancer Sci. 2009 Dec;100(12):2283-91. doi: 10.1111/j.1349-7006.2009.01313.x. Epub 2009 Aug 17.
Colorectal carcinoma (CRC) is often lethal when invasion and/or metastasis occur. 15-Lipoxygenase-1 (15-LO-1), a member of the inflammatory eicosanoid pathway, oxidatively metabolizes linoleic acid and its expression is repressed in CRC. In this study, we investigated the hypothesis that the lack of 15-LO-1 expression in CRC cells might contribute to tumorigenesis. Therefore we introduced 15-LO-1 into HCT-116 and HT-29 cells that do not have detectable levels of 15-LO-1. Our data indicate that expression of 15-LO-1 significantly decreased cell proliferation and increased apoptosis. In addition, we observed a reduction in adhesion to fibronectin, anchorage-independent growth on soft agar, cellular motility and ability to heal a scratch wound, and migratory and invasive capacity across Matrigel. 15-LO-1 expression also reduced the expression of metastasis associated protein-1, a part of the nucleosome remodeling and histone deacetylase silencing complex. We propose that 15-LO-1 expression in CRC might contribute to the inhibition of metastatic capacity in vitro and can be exploited for therapeutic purposes.
结直肠癌(CRC)在发生侵袭和/或转移时往往是致命的。15-脂氧合酶-1(15-LO-1)是炎症类二十烷素途径的成员,它氧化代谢亚油酸,在 CRC 中表达受到抑制。在这项研究中,我们假设 CRC 细胞中 15-LO-1 的缺乏可能导致肿瘤发生。因此,我们将 15-LO-1 引入缺乏 15-LO-1 检测水平的 HCT-116 和 HT-29 细胞中。我们的数据表明,15-LO-1 的表达显著降低了细胞增殖并增加了细胞凋亡。此外,我们观察到细胞对纤维连接蛋白的黏附性降低、软琼脂上的锚定非依赖性生长、细胞迁移能力和伤口愈合能力以及穿过 Matrigel 的迁移和侵袭能力降低。15-LO-1 的表达还降低了核小体重塑和组蛋白去乙酰化沉默复合物的一部分——转移相关蛋白-1 的表达。我们提出,CRC 中的 15-LO-1 表达可能有助于抑制体外转移能力,并可用于治疗目的。