IKKβ在炎症与肿瘤中的作用

Function of IκB kinase links inflammation and cancer

1863年病理学鼻祖Rudolf Virchow在肿瘤组织中发现了白细胞,并称肿瘤来源于有慢性炎症的区域[1].随着对肿瘤微环境的不断认识,其中含有各种免疫细胞,能分泌促进炎症的细胞因子和趋化因子,如TNFα,IL-1,IL-6,IL-8,基质降解酶和氧自由基等,这些都是造成DNA损伤的因素[2].在如此错综复杂的微环境中,细胞增殖、存活、迁移、血管新生,从而促进了肿瘤的发生.炎症与肿瘤作为两大基本病理变化,两者之间存在密切联系,长久以来已被公认,如慢性宫颈炎与宫颈癌,慢性肝炎与肝癌,溃疡性结肠炎与结肠癌等,但对其分子机制的认识却寥寥无几.近年来掀起对核转录因子NF-κB的研究热潮,确立了NF-κB在炎症反应中的中心地位[3],从而为研究炎症与肿瘤分子联系提供了一个切入点.

It has long been acknowledged that there is a link between inflammation and cancer, but its molecular mechanism remains unclear. A key player in inflammation is nuclear transcription factor NF - κB, that activity is triggered in response to infectious agents and proinflammatory cytokines via the boB kinase. In parenchyma cells, inflammation through boB kinase/NF - κB pathway suppresses apoptosis, accelerates cell cycle, then promote tumorigenesis. In mesenchyma cells inflammation through boB kinase/NF - κB pathway produces cytokines and chemokines that may serve as tumor growth factors. To sum up, IκB kinase/NF - κB pathway represents a critical molecular link between inflammation and cancer.