Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Curr Cancer Drug Targets. 2011 Jun;11(5):560-71. doi: 10.2174/156800911795655958.
It is strongly established by numerous studies that oxidative stress-induced inflammation is one of the major causative agents in a variety of cancers. Various factors such as bacterial, viral, parasitic infections, chemical irritants, carcinogens are involved in the initiation of oxidative stress-mediated inflammation. Chronic and persistent inflammation promotes the formation of cancerous tumors. Recent investigations strongly suggest that aldose reductase [AR; AKR1B1], a member of aldo-keto reductase superfamily of proteins, is the mediator of inflammatory signals induced by growth factors, cytokines, chemokines, carcinogens etc. Further, AR reduced product(s) of lipid derived aldehydes and their metabolites such as glutathionyl 1,4-dihydroxynonanol (GS-DHN) have been shown to be involved in the activation of transcription factors such as NF-κB and AP-1 which transcribe the genes of inflammatory cytokines. The increased inflammatory cytokines and growth factors promote cell proliferation, a main feature involved in the tumorigenesis process. Inhibition of AR has been shown to prevent cancer cell growth in vitro and in vivo models. In this review, we have described the possible association between AR with oxidative stress- and inflammation- initiated carcinogenesis. A thorough understanding of the role of AR in the inflammation -associated cancers could lead to the use of AR inhibitors as novel chemotherapeutic agents against cancer.
大量研究证实，氧化应激诱导的炎症是多种癌症的主要致病因素之一。细菌、病毒、寄生虫感染、化学刺激物、致癌物质等各种因素都参与了氧化应激介导的炎症的启动。慢性和持续性炎症促进了癌性肿瘤的形成。最近的研究强烈表明，醛糖还原酶[AR；AKR1B1]是生长因子、细胞因子、趋化因子、致癌物质等诱导的炎症信号的介质。此外，已经表明 AR 还原的脂质衍生醛及其代谢物（如谷胱甘肽基 1,4-二羟壬醇（GS-DHN））参与转录因子如 NF-κB 和 AP-1 的激活，这些转录因子转录炎症细胞因子的基因。增加的炎症细胞因子和生长因子促进细胞增殖，这是肿瘤发生过程中的一个主要特征。本综述描述了 AR 与氧化应激和炎症引发的致癌作用之间的可能关联。深入了解 AR 在炎症相关癌症中的作用可能导致使用 AR 抑制剂作为新型化疗药物来对抗癌症。
