一氧化氮释放型非甾体抗炎药（NO-NSAIDs）对黑素瘤细胞黏附的影响。
Effects of nitric oxide-releasing nonsteroidal anti-inflammatory drugs (NONO-NSAIDs) on melanoma cell adhesion.
机构信息
Edison Biotechnology Institute, Ohio University, Athens, OH 45701, USA.
出版信息
Toxicol Appl Pharmacol. 2012 Oct 15;264(2):161-6. doi: 10.1016/j.taap.2012.07.029. Epub 2012 Aug 4.
A new class of nitric oxide (NO•)-releasing nonsteroidal anti-inflammatory drugs (NONO-NSAIDs) were developed in recent years and have shown promising potential as NSAID substitutes due to their gentle nature on cardiovascular and gastrointestinal systems. Since nitric oxide plays a role in regulation of cell adhesion, we assessed the potential use of NONO-NSAIDs as anti-metastasis drugs. In this regard, we compared the effects of NONO-aspirin and a novel NONO-naproxen to those exerted by their respective parent NSAIDs on avidities of human melanoma M624 cells. Both NONO-NSAIDs, but not the corresponding parent NSAIDs, reduced M624 adhesion on vascular cellular adhesion molecule-1 (VCAM-1) by 20-30% and fibronectin by 25-44% under fluid flow conditions and static conditions, respectively. Only NONO-naproxen reduced (~56%) the activity of β1 integrin, which binds to α4 integrin to form very late antigen-4 (VLA-4), the ligand of VCAM-1. These results indicate that the diazeniumdiolate (NO•)-donor moiety is critical for reducing the adhesion between VLA-4 and its ligands, while the NSAID moiety can impact the regulation mechanism of melanoma cell adhesion.
近年来，人们开发了一类新型的一氧化氮（NO•）释放型非甾体抗炎药（NONO-NSAIDs），由于其对心血管和胃肠道系统的温和特性，它们作为 NSAID 的替代品具有很大的潜力。由于一氧化氮在细胞黏附的调节中发挥作用，我们评估了 NONO-NSAIDs 作为抗转移药物的潜在用途。在这方面，我们比较了 NONO-阿司匹林和新型 NONO-萘普生与各自的母体 NSAIDs 对人类黑色素瘤 M624 细胞活力的影响。两种 NONO-NSAIDs（而非相应的母体 NSAIDs）均可分别在流体流动条件和静态条件下，将 M624 细胞在血管细胞黏附分子-1（VCAM-1）上的黏附性降低 20-30%和 25-44%，将黏附在纤维连接蛋白上的黏附性降低 20-30%和 25-44%。只有 NONO-萘普生降低了β1 整合素的活性（~56%），β1 整合素结合到α4 整合素上形成非常晚抗原-4（VLA-4），VLA-4 是 VCAM-1 的配体。这些结果表明，叠氮二硝酸盐（NO•）供体部分对于降低 VLA-4 与其配体之间的黏附至关重要，而 NSAID 部分可以影响黑色素瘤细胞黏附的调节机制。
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