Norwood Stephanie, Liao Jie, Hammock Bruce D, Yang Guang-Yu
Am J Transl Res. 2010 Jul 22;2(4):447-57.
Chronic inflammation is an important factor contributing to human carcinoma, and non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to have a preventive effect in the development of various types of carcinoma. However, NSAIDs also have adverse side effects including increased cardiovascular events, making them less than ideal for routine chemoprevention. Soluble epoxide hydrolase (sEH) is an enzyme that converts endogenous anti-inflammatory compounds, the epoxyeicosatrienoic acids (EETs), to the less anti-inflammatory dihydroxyeicosatrienoic acids (DHETs). Inhibition of sEH, by a highly selective and potent sEH inhibitor (sEHI), increases EETs leading to decreased inflammation. In our studies, administration of a sEHI in mouse colitis models led to decreased ulcer incidence and number of ulcers compared to controls, with no adverse side effects seen. In human tissue, sEH showed an increase in expression, as seen immunohistochemically, in ulcerative colitis (UC), UC-induced dysplasia, and UC-induced carcinoma. Thus, inhibition of sEH may be a novel biomarker and potential therapeutic target in inflammation and inflammation-induced carcinoma.
慢性炎症是导致人类癌症的一个重要因素，并且非甾体抗炎药（NSAIDs）已被证明在各类癌症的发生发展中具有预防作用。然而，NSAIDs也有不良副作用，包括心血管事件增加，这使得它们对于常规化学预防而言并不理想。可溶性环氧化物水解酶（sEH）是一种将内源性抗炎化合物环氧二十碳三烯酸（EETs）转化为抗炎性较弱的二羟基二十碳三烯酸（DHETs）的酶。通过高选择性和强效的sEH抑制剂（sEHI）抑制sEH，会增加EETs，从而减轻炎症。在我们的研究中，与对照组相比，在小鼠结肠炎模型中给予sEHI可降低溃疡发生率和溃疡数量，且未见不良副作用。在人体组织中，通过免疫组织化学观察发现，sEH在溃疡性结肠炎（UC）、UC诱导的发育异常以及UC诱导的癌症中表达增加。因此，抑制sEH可能是炎症及炎症诱导癌症中的一种新型生物标志物和潜在治疗靶点。
