Liu-Smith Feng, Dellinger Ryan, Meyskens Frank L
Department of Epidemiology, University of California School of Medicine, Irvine, CA 92697, United States; Department of Medicine, University of California School of Medicine, Irvine, CA 92697, United States; Chao Family Comprehensive Cancer Center, University of California School of Medicine, Irvine, CA 92697, United States.
Department of Medicine, University of California School of Medicine, Irvine, CA 92697, United States; Chao Family Comprehensive Cancer Center, University of California School of Medicine, Irvine, CA 92697, United States.
Arch Biochem Biophys. 2014 Dec 1;563:51-5. doi: 10.1016/j.abb.2014.04.007. Epub 2014 Apr 26.
Reactive oxygen species (ROS) play crucial roles in all aspects of melanoma development, however, the source of ROS is not well defined. In this review we summarize recent advancement in this rapidly developing field. The cellular ROS pool in melanocytes can be derived from mitochondria, melanosomes, NADPH oxidase (NOX) family enzymes, and uncoupling of nitric oxide synthase (NOS). Current evidence suggests that Nox1, Nox4 and Nox5 are expressed in melanocytic lineage. While there is no difference in Nox1 expression levels in primary and metastatic melanoma tissues, Nox4 expression is significantly higher in a subset of metastatic melanoma tumors as compared to the primary tumors; suggesting distinct and specific signals and effects for NOX family enzymes in melanoma. Targeting these NOX enzymes using specific NOX inhibitors may be effective for a subset of certain tumors. ROS also play important roles in BRAF inhibitor induced drug resistance; hence identification and blockade of the source of this ROS may be an effective way to enhance efficacy and overcome resistance. Furthermore, ROS from different sources may interact with each other and interact with reactive nitrogen species (RNS) and drive the melanomagenesis process at all stages of disease. Further understanding ROS and RNS in melanoma etiology and progression is necessary for developing new prevention and therapeutic approaches.
活性氧（ROS）在黑色素瘤发展的各个方面都起着至关重要的作用，然而，ROS的来源尚未明确界定。在本综述中，我们总结了这一快速发展领域的最新进展。黑素细胞中的细胞ROS池可源自线粒体、黑素小体、NADPH氧化酶（NOX）家族酶以及一氧化氮合酶（NOS）的解偶联。目前的证据表明，Nox1、Nox4和Nox5在黑素细胞谱系中表达。虽然原发性和转移性黑色素瘤组织中Nox1的表达水平没有差异，但与原发性肿瘤相比，Nox4在一部分转移性黑色素瘤肿瘤中的表达明显更高；这表明NOX家族酶在黑色素瘤中具有独特且特定的信号和作用。使用特定的NOX抑制剂靶向这些NOX酶可能对某些特定肿瘤有效。ROS在BRAF抑制剂诱导的耐药性中也起重要作用；因此，识别并阻断这种ROS的来源可能是提高疗效和克服耐药性的有效方法。此外，来自不同来源的ROS可能相互作用，并与活性氮物质（RNS）相互作用，在疾病的各个阶段推动黑色素瘤的发生发展过程。进一步了解黑色素瘤病因和进展中的ROS和RNS对于开发新的预防和治疗方法是必要的。
