Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226, USA.
Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Int J Mol Sci. 2018 Jan 6;19(1):166. doi: 10.3390/ijms19010166.
Early inhibition of inflammation suppresses the carcinogenic process. Aspirin is the most commonly used non-steroid anti-inflammatory drugs (NSAIDs), and it irreversibly inhibits cyclooxygenase-1 and -2 (COX1, COX2). Multiple randomized clinical trials have demonstrated that aspirin offers substantial protection from colon cancer mortality. The lower aspirin doses causing only minimal gastrointestinal disturbance, ideal for long-term use, can achieve only partial and transitory inhibition of COX2. Aspirin's principal metabolite, salicylic acid, is also found in fruits and vegetables that inhibit COX2. Other phytochemicals such as curcumin, resveratrol, and anthocyanins also inhibit COX2. Such dietary components are good candidates for combination with aspirin because they have little or no toxicity. However, obstacles to using phytochemicals for chemoprevention, including bioavailability and translational potential, must be resolved. The bell/U-shaped dose-response curves seen with vitamin D and resveratrol might apply to other phytochemicals, shedding doubt on 'more is better'. Solutions include: (1) using special delivery systems (e.g., nanoparticles) to retain phytochemicals; (2) developing robust pharmacodynamic biomarkers to determine efficacy in humans; and (3) selecting pharmacokinetic doses relevant to humans when performing preclinical experiments. The combination of aspirin and phytochemicals is an attractive low-cost and low-toxicity approach to colon cancer prevention that warrants testing, particularly in high-risk individuals.
早期抑制炎症可抑制致癌过程。阿司匹林是最常用的非甾体抗炎药（NSAIDs），它可不可逆地抑制环氧化酶-1 和 -2（COX1、COX2）。多项随机临床试验表明，阿司匹林可显著降低结肠癌死亡率。较低剂量的阿司匹林仅引起轻微的胃肠道不适，适合长期使用，只能对 COX2 产生部分和短暂的抑制作用。阿司匹林的主要代谢产物水杨酸也存在于抑制 COX2 的水果和蔬菜中。其他植物化学物质，如姜黄素、白藜芦醇和花青素，也可抑制 COX2。这些膳食成分是与阿司匹林联合使用的良好候选物，因为它们毒性很小或没有毒性。但是，在将植物化学物质用于化学预防方面仍存在障碍，包括生物利用度和转化潜力，必须加以解决。维生素 D 和白藜芦醇的钟形/倒 U 形剂量反应曲线可能适用于其他植物化学物质，这对“越多越好”的观点提出了质疑。解决方案包括：（1）使用特殊的输送系统（例如纳米颗粒）保留植物化学物质；（2）开发强大的药效动力学生物标志物以确定在人类中的疗效；（3）在进行临床前实验时，选择与人类相关的药代动力学剂量。阿司匹林和植物化学物质的联合使用是一种具有吸引力的低成本、低毒性的结肠癌预防方法，值得进一步研究，尤其是在高危人群中。
