Harrison Ian P, Selemidis Stavros
Department of Pharmacology, Monash University, Melbourne, Vic., Australia.
Clin Exp Pharmacol Physiol. 2014 Aug;41(8):533-42. doi: 10.1111/1440-1681.12238.
Reactive oxygen species (ROS), the cellular products of myriad physiological processes, have long been understood to lead to cellular damage if produced in excess and to be a causative factor in cancer through the oxidation and nitration of various macromolecules. Reactive oxygen species influence various hallmarks of cancer, such as cellular proliferation and angiogenesis, through the promotion of cell signalling pathways intrinsic to these processes and can also regulate the function of key immune cells, such as macrophages and regulatory T cells, which promote angiogenesis in the tumour environment. Herein we emphasize the family of NADPH oxidase enzymes as the most likely source of ROS, which promote angiogenesis and tumourigenesis through signalling pathways within endothelial, immune and tumour cells. In this review we focus on the pharmacological inhibitors of NADPH oxidases and suggest that, compared with traditional anti-oxidants, they are likely to offer better alternatives for suppression of tumour angiogenesis. Despite the emerging enthusiasm towards the use of NADPH oxidase inhibitors for cancer therapy, this field is still in its infancy; in particular, there is a glaring lack of knowledge of the roles of NADPH oxidases in in vivo animal models and in human cancers. Certainly a clearer understanding of the relevant signalling pathways influenced by NADPH oxidases during angiogenesis in cancer is likely to yield novel therapeutic approaches.
活性氧（ROS）是众多生理过程的细胞产物，长期以来人们一直认为，如果过量产生，ROS会导致细胞损伤，并通过氧化和硝化各种大分子成为癌症的致病因素。活性氧通过促进这些过程固有的细胞信号通路来影响癌症的各种特征，如细胞增殖和血管生成，还可以调节关键免疫细胞（如巨噬细胞和调节性T细胞）的功能，这些细胞在肿瘤环境中促进血管生成。在此，我们强调NADPH氧化酶家族是ROS最可能的来源，其通过内皮细胞、免疫细胞和肿瘤细胞内的信号通路促进血管生成和肿瘤发生。在这篇综述中，我们聚焦于NADPH氧化酶的药理抑制剂，并表明，与传统抗氧化剂相比，它们可能为抑制肿瘤血管生成提供更好的选择。尽管人们对使用NADPH氧化酶抑制剂进行癌症治疗的热情日益高涨，但该领域仍处于起步阶段；特别是，对于NADPH氧化酶在体内动物模型和人类癌症中的作用，人们仍知之甚少。当然，更清楚地了解NADPH氧化酶在癌症血管生成过程中影响的相关信号通路，可能会产生新的治疗方法。
