【摘要】 目前,癌症是全球第二大死亡人数最多的疾病。炎症反应是一个复杂的生理学过程,涉及到生物体中细胞以及分子层面的广泛变化。在组织修复,伤口愈合以及抵御外来病原体入侵的过程中,有序的炎症反应是机体免疫系统产生的正常防御反应,保证机体的健康。但当这种急性炎症持续较长时间且得不到有效控制时,就易发展成慢性炎症,从而促进许多疾病的发生,包括风湿性关节炎,心血管疾病,阿尔茨海默症和癌症等。越来越多的证据表明,炎症反应失调在癌症中起到关键作用,长期使用非甾体类抗炎药(Non-steroidal anti-inflammatory drugs,NSAIDs)可以降低多种癌症的发病率。文章重点综述了核因子-κB(Nuclear factor-kappa B,NF-κB)在炎癌中的复杂作用,包括NF-κB对炎症反应具有的正向和负向调节作用,以及它如何影响肿瘤的发生和发展。深度解析NF-κB在炎-癌转化中的作用对于现代肿瘤生物学来说是一个重要挑战。更多还原

【Abstract】 Cancer is the second largest leading cause of death in the world. Inflammation is a complex physiological process that involves an extensive variation at cell and molecular levels of organisms. In the process of tissue repair,wound healing,and defense against the invasion of foreign pathogens,inflammation is a normal defensive response of the host immune cells including macrophages and monocytes. Besides defensive response ensures the health of the body. However,if it is not ordered and timely,the resulting chronic inflammation can contribute to various diseases such as periodontitis,rheumatoid arthritis,Alzheimer’s disease and cancer. Nowadays it is generally accepted that at least 15% of cancer is caused by chronic inflammation. Increasing evidence from epigenetic,preclinical and clinical studies suggests that dysregulated inflammatory response plays a pivotal role in cancer and long-term use of non-steroidal anti-inflammatory drugs( NSAIDs) reduces the risk of several cancers. NF-κB,is an important transcriptional factor,which forms an inactive complex with its inhibitor of κB( IκB). Upon stimulation to cells with corresponding ligands,such as LPS,IL-1β or TNFα,the IκB kinase( IKK) complex is activated,which leads to the phosphorylation and degradation of IκB,then allows the translocation of NF-κB into the nucleus and binds to specific DNA sequences in target genes,thereby it can regulate transcription levels of over 400 genes involved in inflammation,immunoregulation,programmed cell death,tumor cell proliferation,growth arrest,invasion,metastasis,angiogenesis,chemoresistance and radioresistance. It is an important link between inflammation and tumorigenesis. This study reviews the complex function of the transcription factor NF-κB in linking inflammation to cancer,including the positive and negative roles of NF-κB in the control inflammation responses and how these opposing functions affect tumor development and progression. Clearly understanding the function of NF-κB in the context of inflammation-tumorigenesis is a critical challenge for modern cancer biology.更多还原