乙酰水杨酸及其对结直肠癌的化学预防潜力。

Podhorec Ján, Hrstka Roman, Bílek Ondřej, Tuček Štěpán, Navrátil Jiří, Michalová Eva, Vojtěšek Bořivoj

Klin Onkol. 2018 Winter;31(Suppl 2):77-81. doi: 10.14735/amko20182S77.

BACKGROUND

Non-steroidal anti-inflammatory drugs (NSAID) represent a group of medicaments inhibiting cyclooxygenase (COX) enzyme, and, in parallel, these drugs show also analgesic, antipyretic and anti-inflammatory effects. Due to their efficiency, good tolerance and easy availability, they belong to the worlds most used drugs. For decades, evidence of their anti-tumor activity has been growing, with the largest amount of published work being related to colorectal cancer (CRC). Based on both in vitro and in vivo experiments and data obtained from epidemiological and clinical studies, potential application of NSAID as chemo-preventive treatment for CRC patients is recently discussed in order to prevent development or recurrence of precanceroses and tumors. Promising treatment for such indication would be acetylsalicylic acid (ASA), which is the oldest, more than 100 years used member of the NSAID family. Nonselective irreversible COX inhibition is an important but probably not solely mechanism of its anticancer activity. Notably, wider use of ASA in chemoprevention is also prevented due to particular concerns about gastrointestinal and renal toxicity caused especially by its long-term use.

AIMS

This review introduces the role of COX in tumor biology of CRC and highlights the results of the most interesting experiments illustrating the anti-tumor effect of ASA. Moreover, our work evaluates the most important published clinical analyzes of the ASA chemopreventive effect on CRC and discusses the current state. Key words: non-steroidal anti-inflammatory agents - acetylsalicylic acid - colorectal carcinoma - cyclooxygenase - chemoprevention This work was supported by the projects MEYS - NPS I - LO1413, MH CZ - DRO (MMCI, 00209805) and by Czech Science Foundation project no. 16-14829S. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Accepted: 10. 9. 2017.

背景

非甾体抗炎药（NSAID）是一类抑制环氧化酶（COX）的药物，同时还具有镇痛、解热和抗炎作用。因其疗效好、耐受性佳且易于获取，它们是全球使用最为广泛的药物之一。几十年来，其抗肿瘤活性的证据不断增加，其中发表量最多的研究与结直肠癌（CRC）相关。基于体外和体内实验以及从流行病学和临床研究中获得的数据，近期人们讨论了NSAID作为CRC患者化学预防治疗手段的潜在应用，以预防癌前病变和肿瘤的发生或复发。针对这一适应症，有前景的治疗药物可能是乙酰水杨酸（ASA），它是NSAID家族中使用历史最久、已应用超过100年的药物。非选择性不可逆COX抑制是其抗癌活性的一个重要机制，但可能并非唯一机制。值得注意的是，由于长期使用ASA尤其会引发胃肠道和肾脏毒性，人们对其在化学预防中的更广泛应用也有所顾虑。

目的

本综述介绍了COX在CRC肿瘤生物学中的作用，并着重阐述了最具意义的实验结果，这些实验证实了ASA的抗肿瘤作用。此外，我们的研究评估了已发表的关于ASA对CRC化学预防作用的最重要临床分析，并探讨了当前的研究现状。关键词：非甾体抗炎药 - 乙酰水杨酸 - 结直肠癌 - 环氧化酶 - 化学预防本研究得到了MEYS - NPS I - LO1413、MH CZ - DRO（MMCI，00209805）项目以及捷克科学基金会第16 - 14829S号项目的支持。作者声明他们在研究中使用的药物、产品或服务不存在潜在利益冲突。编辑委员会声明该手稿符合ICMJE对生物医学论文的要求。接受日期：2017年9月10日。