Sahebnasagh Adeleh, Saghafi Fatemeh, Negintaji Sina, Hu Tingyan, Shabani-Borujeni Mojtaba, Safdari Mohammadreza, Ghaleno Hassan Rezai, Miao Lingchao, Qi Yaping, Wang Mingfu, Liao Pan, Sureda Antoni, Simal-Gándara Jesus, Nabavi Seyed Mohammad, Xiao Jianbo
Clinical Research Center, Department of Internal Medicine, Faculty of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran.
Department of Clinical Pharmacy, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Curr Med Chem. 2022;29(9):1561-1595. doi: 10.2174/0929867328666210707194543.
In recent years, there has been an increasing interest in understanding the mysterious functions of nitric oxide (NO) and how this pleiotropic signaling molecule contributes to tumorigenesis. This review attempts to expose and discuss the information available on the immunomodulatory role of NO in cancer and recent approaches to the role of NO donors in the area of immunotherapy. To address the goal, the following databases were searched to identify relevant literature concerning empirical evidence: The Cochrane Library, Pubmed, Medline, and EMBASE from 1980 through March 2020. Valuable attempts have been made to develop distinctive NO-based cancer therapy. Although the data do not allow generalization, the evidence seems to indicate that low/moderate levels may favor tumorigenesis, while higher levels would exert antitumor effects. In this sense, the use of NO donors could have an important therapeutic potential within immunotherapy, although there are still no clinical trials. The emerging understanding of NO-regulated immune responses in cancer may help unravel the recent features of this "doubleedged sword" in cancer physiological and pathologic processes and its potential use as a therapeutic agent for cancer treatment. In short, in this review, we discuss the complex cellular mechanism in which NO, as a pleiotropic signaling molecule, participates in cancer pathophysiology. We also debate the dual role of NO in cancer and tumor progression and clinical approaches for inducible nitric oxide synthase (iNOS) based therapy against cancer.
近年来，人们对了解一氧化氮（NO）的神秘功能以及这种多效性信号分子如何促进肿瘤发生越来越感兴趣。本综述试图揭示并讨论关于NO在癌症中的免疫调节作用以及NO供体在免疫治疗领域作用的现有信息。为实现这一目标，检索了以下数据库以识别有关实证证据的相关文献：1980年至2020年3月的考克兰图书馆、PubMed、Medline和EMBASE。人们已做出宝贵尝试来开发独特的基于NO的癌症治疗方法。尽管数据无法一概而论，但证据似乎表明低/中等水平可能有利于肿瘤发生，而较高水平则会发挥抗肿瘤作用。从这个意义上说，NO供体的使用在免疫治疗中可能具有重要的治疗潜力，尽管目前尚无临床试验。对癌症中NO调节的免疫反应的新认识可能有助于揭示这种“双刃剑”在癌症生理和病理过程中的最新特征及其作为癌症治疗药物的潜在用途。简而言之，在本综述中，我们讨论了NO作为多效性信号分子参与癌症病理生理学的复杂细胞机制。我们还讨论了NO在癌症和肿瘤进展中的双重作用以及基于诱导型一氧化氮合酶（iNOS）的癌症治疗的临床方法。
