Aspirin and the potential role of prostaglandins in colon cancer.
Aspirin and the potential role of prostaglandins in colon cancer.
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作者：
L. Marnett
花生四烯酸级联反应产生一系列生物活性脂质，调节不同的生理和病理生理反应。尽管花生四烯酸代谢产物在癌症中的作用引起了人们的极大兴趣，但关于哪些代谢产物是最重要的，以及它们如何在细胞转化、肿瘤生长和转移的特定步骤中起作用仍是不确定的(1-9)。花生四烯酸代谢的复杂性令新手望而生畏，而单一代谢物施加的多重反应可能会使已知的人感到困惑。这使得很难将动物实验的结果外推到人类身上。Thun等人最近的一份报告。(10)和Rune等人之前的报告。(11)和Rosenberg等人。(12)表明摄入阿司匹林可以降低普通人群中结肠癌的发病率(11，12)和死亡率(10)。Paganini-Hill等人的其他研究。(13、14)不支持这样的联合。阿司匹林是花生四烯酸级联反应的一个分支的相对特异的抑制剂，尽管在这些流行病学调查中并没有普遍的共识，但他们的发现重新将注意力集中在花生四烯酸代谢产物在癌症中的作用上。这一观点是为了突出一些关于花生四烯酸级联反应中可抑制阿司匹林的分支与癌症的现有文献，尽可能将其应用于结肠癌，并找出我们知识中需要解决的不足。虽然主要的焦点是结肠，但机械概念应该适用于其他器官部位。本透视从花生四烯酸代谢的概述开始，进而考虑阿司匹林抑制的酶的生化和分子生物学，触及与花生四烯酸代谢有关的信号转导途径，然后考虑特定的花生四烯酸代谢产物参与致癌过程的机制。审查的目的不是要全面，对工作没有突出或无意中遗漏的同事提前道歉。
The arachidonic acid cascade generates a family of bioactive lipids that modulate diverse physiological and pathophysiological responses. Although there has been a great deal of interest in the involvement of arachidonic acid metabolites in cancer, there is uncertainty about which metabolites are the most im portant and how they contribute to specific steps in cell trans formation, tumor growth, and metastasis (1-9). The complex ity of arachidonic acid metabolism is daunting to neophytes and the multiplicity of responses exerted by a single metabolite can be confusing to the cognoscenti. This has made it difficult to extrapolate results from animal experiments to human beings. A recent report from Thun et al. (10) and previous reports from Rune et al. (11) and Rosenberg et al. (12) suggest that aspirin intake may reduce colon cancer incidence (11, 12) and mortality (10) in the general population. Other studies from Paganini-Hill et al. (13, 14) do not support such an association. Aspirin is a relatively specific inhibitor of one branch of the arachidonic acid cascade and even though there is not universal agreement among these epidemiological investigations, their findings refocus attention on the role of arachidonic acid me tabolites in cancer. This Perspective was written to highlight some of the existing literature on the aspirin-inhibitable branch of the arachidonic acid cascade and cancer, to apply that liter ature to colon cancer where possible, and to identify deficien cies in our knowledge that need to be addressed. Although the major focus is the colon, the mechanistic concepts should be applicable to other organ sites. The Perspective begins with an overview of arachidonic acid metabolism, proceeds to a consideration of the biochemistry and molecular biology of the enzyme inhibited by aspirin, touches on the signal transduction pathways linked to arachi donic acid metabolism, and then considers mechanisms by which specific arachidonic acid metabolites participate in the carcinogenic process. The review is not meant to be compre hensive and apologies are made in advance to colleagues whose work is not highlighted or was inadvertantly omitted.