5-氨基水杨酸通过调节环氧化酶-2 和 15-羟基前列腺素脱氢酶的表达抑制结直肠肿瘤发生。
5-aminosalicylic acid mediates expression of cyclooxygenase-2 and 15-hydroxyprostaglandin dehydrogenase to suppress colorectal tumorigenesis.
机构信息
Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
出版信息
Anticancer Res. 2012 Apr;32(4):1193-202.
BACKGROUND
Cyclooxygenase-2 (COX-2) is a key enzyme that produces prostaglandin E2 (PGE2) and plays an important role in colorectal tumor growth. In addition, recent researches focused on 15-hydroxyprostaglandin dehydrogenase (15-PGDH), which degrades PGE2. Here we determined the effect of 5-aminosalicylic acid (5-ASA) on COX-2 and 15-PGDH expression and investigated its preventive effect for colorectal cancer (CRC).
MATERIALS AND METHODS
HT-29 cells were used in the in vitro experiments. c-Ha-ras transgenic mice were employed in order to explore the chemopreventive effects. Western blotting analysis was performed and the protein expression of COX-2 and 15-PGDH was quantified.
RESULTS
5-ASA significantly suppressed COX-2 expression and induced 15-PGDH expression in HT-29 cells. In the transgenic mice, oral 5-ASA intake reduced the incidence of colorectal tumor formation and the tumor size. Furthermore, we observed a down-regulation of COX-2 and an up-regulation of 15-PGDH in the tissue from colons of these mice.
CONCLUSION
5-ASA exerts a preventive effect against colorectal tumor development through mediation of COX-2 and 15-PGDH expression.
背景
环氧化酶-2（COX-2）是一种产生前列腺素 E2（PGE2）的关键酶，在结直肠肿瘤生长中发挥重要作用。此外，最近的研究集中在 15-羟基前列腺素脱氢酶（15-PGDH）上，它可以降解 PGE2。在这里，我们确定了 5-氨基水杨酸（5-ASA）对 COX-2 和 15-PGDH 表达的影响，并研究了其对结直肠癌（CRC）的预防作用。
材料和方法
在体外实验中使用 HT-29 细胞。为了探索化学预防作用，使用 c-Ha-ras 转基因小鼠。进行 Western blot 分析，并定量 COX-2 和 15-PGDH 的蛋白表达。
结果
5-ASA 可显著抑制 HT-29 细胞中的 COX-2 表达并诱导 15-PGDH 表达。在转基因小鼠中，口服 5-ASA 摄入可降低结直肠肿瘤形成的发生率和肿瘤大小。此外，我们观察到这些小鼠结肠组织中 COX-2 的下调和 15-PGDH 的上调。
结论
5-ASA 通过调节 COX-2 和 15-PGDH 的表达对结直肠肿瘤的发生发展具有预防作用。
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