Chan Timothy A
Johns Hopkins Oncology Center, Johns Hopkins University, Baltimore, MD 21231, USA.
Lancet Oncol. 2002 Mar;3(3):166-74. doi: 10.1016/s1470-2045(02)00680-0.
Nonsteroidal anti-inflammatory drugs (NSAIDs) can inhibit colorectal tumorigenesis and are among the few agents known to be chemopreventive. Epidemiological studies and experiments with animals have shown that NSAIDs have powerful anticolorectal cancer properties, but the mechanism of these effects remains unclear. NSAIDs can inhibit neoplastic growth by inducing apoptosis in cancer cells; the way they do this is currently an area of intense investigation. The most well-characterised pharmacological feature of NSAIDs is their inhibition of the enzyme cyclo-oxygenase (COX), which catalyses the synthesis of prostaglandins. Several studies have shown that COX inhibition prevents cell proliferation and promotes apoptosis. The chemopreventive effects of NSAIDs are thought to occur via this pathway. Other observations indicate that NSAIDs also promote apoptosis through mechanisms that are independent of COX inhibition. This idea is supported by the finding that compounds that are structurally similar to NSAIDs, but do not inhibit COX, also have chemopreventive and proapoptotic properties. COX-dependent and COX-independent mechanisms of apoptosis induction are not mutually exclusive, and it is likely that both have a role in the biological activity of NSAIDs. Knowledge of how NSAIDs prevent neoplastic growth will greatly aid the design of better chemopreventive drugs and novel treatments for colorectal cancer.
非甾体抗炎药（NSAIDs）能够抑制结直肠癌的发生，是已知的少数具有化学预防作用的药物之一。流行病学研究和动物实验表明，NSAIDs具有强大的抗结直肠癌特性，但其作用机制仍不清楚。NSAIDs可通过诱导癌细胞凋亡来抑制肿瘤生长；目前这一作用方式是深入研究的领域。NSAIDs最具特征的药理学特性是其对环氧化酶（COX）的抑制作用，COX可催化前列腺素的合成。多项研究表明，抑制COX可阻止细胞增殖并促进凋亡。NSAIDs的化学预防作用被认为是通过这一途径发生的。其他观察结果表明，NSAIDs还可通过独立于COX抑制作用的机制促进凋亡。这一观点得到以下发现的支持：结构与NSAIDs相似但不抑制COX的化合物也具有化学预防和促凋亡特性。依赖COX和不依赖COX的凋亡诱导机制并非相互排斥，二者可能都在NSAIDs的生物学活性中发挥作用。了解NSAIDs如何预防肿瘤生长将极大地有助于设计出更好的化学预防药物和结直肠癌的新型治疗方法。
