Levy G N
Department of Pharmacology, University of Michigan, Ann Arbor 48109-0632, USA.
FASEB J. 1997 Mar;11(4):234-47.
Members of the structurally diverse class of drugs known as nonsteroidal anti-inflammatory drugs (NSAIDs) have the ability to prevent or reduce the occurrence of colorectal, certain other gastrointestinal, and perhaps other cancers. The anticarcinogenic property of NSAIDs has been shown in epidemiological studies with humans and in experimental carcinogenesis studies with animals. In addition, clinical studies of the human disease familial adenomatous polyposis have demonstrated the efficacy of NSAIDs in mediating regression of colorectal adenomas. The mechanism of the anticarcinogenic effect of these drugs is not known, but most hypotheses have involved the common property of the NSAIDs to inhibit prostaglandin synthase (PHS) enzymes and thereby cause a subsequent reduction in levels of prostaglandins (PG) in tissue. Recent reports have questioned the role of PHS inhibition in the anticarcinogenic activity of NSAIDs by showing that some NSAID-related compounds that are not PHS inhibitors can induce the same anticarcinogenic changes in cell cycle and apoptotic response as the PHS inhibitors. In this review we will examine the evidence that NSAIDs are anticarcinogenic, the evidence supporting PHS as the target of NSAIDs, and the evidence for and against inhibition of PG synthesis as the mechanism of cancer prevention by NSAIDs.
被称为非甾体抗炎药（NSAIDs）的结构多样的一类药物，有能力预防或减少结直肠癌、某些其他胃肠道癌以及可能的其他癌症的发生。NSAIDs的抗癌特性已在人类流行病学研究和动物实验致癌研究中得到证实。此外，对人类疾病家族性腺瘤性息肉病的临床研究表明，NSAIDs在介导结直肠腺瘤消退方面具有疗效。这些药物抗癌作用的机制尚不清楚，但大多数假说都涉及NSAIDs抑制前列腺素合酶（PHS）的共同特性，从而导致组织中前列腺素（PG）水平随后降低。最近的报告对PHS抑制在NSAIDs抗癌活性中的作用提出了质疑，因为研究表明一些非PHS抑制剂的NSAID相关化合物在细胞周期和凋亡反应中能诱导与PHS抑制剂相同的抗癌变化。在本综述中，我们将审视NSAIDs具有抗癌性的证据、支持PHS作为NSAIDs靶点的证据以及支持和反对抑制PG合成作为NSAIDs预防癌症机制的证据。
