芳香烃受体在肿瘤发生及免疫治疗中的作用  

Role of aryl hydrocarbon receptors in tumorigenesis and tumor treatment

作　　者：王翠娟[1] 尚明[2] 邵华[1] WANG Cui-juan;SHANG Ming;SHAO Hua(Department of Laborator,Shandong Academy of Occupational Health and Occupational Medicine,Jinan 250062,P.R.China;Director＇s Office,Shandong Cancer Hospital,Ji＇nan 250117,P.R.China)

机构地区：[1]山东省职业卫生与职业病防治研究院实验室,山东济南250062 [2]山东省肿瘤医院院务部,山东济南250117

出　　处：《中华肿瘤防治杂志》2018年第15期1126-1130,共5页Chinese Journal of Cancer Prevention and Treatment

基　　金：山东省医药卫生科技发展计划(2015WS0167)

摘　　要：目的芳香烃受体(aryl hydrocarbon receptor,AhR)是配体激活型的转录因子,是在研究致癌物二恶英(2,3,7,8-tetrachlorodibenzo-p-dioxin,TCDD)的毒性和致癌作用过程中发现的一种蛋白。本文总结AhR在肿瘤发生、进展等过程的作用以及调控IDO1/TDO2-KYN-AhR信号转导通路在肿瘤治疗中的潜力。方法应用澳大利亚昆士兰大学图书馆英文数据库、PubMed数据库及CNKI中文期刊全文数据库,以"aryl hydrocarbon receptor"、"tryptophan 2,3dioxygenase"、"indoleamine 2,3dioxygenase 1"和"tumor therapy"等作为英文关键词,以"芳香烃受体"、"犬尿氨酸"、"色氨酸2,3-二加氧酶"、"吲哚胺2,3-二加氧酶1"和"肿瘤治疗"等作为中文关键词,检索2000-01-01-2018-1-01的相关文献。纳入标准:(1)芳香烃受体与肿瘤发生、进展关系的研究性文献;(2)IDO1/TDO2-KYN-AhR通路与肿瘤治疗的文献。排除标准:(1)中文非核心期刊的文献和英文非SCI收录的文献;(2)结果重复且相对陈旧的实验研究。最终选择47篇文献纳入分析。结果 AhR可以被内源性激活促进肿瘤的发生和进展;临床试验和动物试验结果表明,以IDO1/TDO1-KYN-AhR信号通路为靶点,通过应用IDO1抑制剂和犬尿氨酸酶可以激活免疫应答、抑制肿瘤的生长,通过应用拮抗剂可以抑制AhR的激活发挥抗癌作用。结论 AhR在肿瘤发生、进展过程中具有重要的作用,调控AHR通路可能成为肿瘤治疗的新靶点。OBJECTIVE To review the current understanding of the role of AhR in tumorigenesis and progression and the potential of IDO1/TDO2-KYN-AhR signal pathway in tumor immunotherapy. METHODS Related literatures be- tween 2000-01-01 to 2018-01-01 were searched in the Library of University of Queensland,PubMed and CNKI series full text databases. The major keywords were aryl hydrocarbon receptor,tryptophan2,3 dioxygenase,indoleamine, 3 dioxygen asel ,and tumor therapy. The adoptive standards were as the following： （1） Research articles related to the role of AhR in the initiation,promotion,progression and metastasis of tumorigenesis. （2） Research articles on the role of IDO1/TD02 KYN-AhR pathway in tumor therapy. The eliminated standards： （1） Non-core journal articles published in Chinese and non-SCI articles published in English. （2） Repeated and relatively old experimental results. A total of 47 literatures were invovled in this review for analysis. RESULTS AhR can be activated endogenously to promote tumorigenesis and pro- gression. In addition,clinical trials and animal studies have shown that IDO1/TDO1-KYN AhR signaling pathways can be used to activate immunization by applying IDOl inhibitors, kynurenase and AhR antagonist. In response, the effect of in- hibiting the growth of the tumor is achieved. CONCLUSION AhR plays an important role in tumorigenesis and progres- sion,and regulation of AHR oathwav may become a new target of tumor immunotheraty.

关 键 词：芳香烃受体 犬尿氨酸 色氨酸2 3-二加氧酶 吲哚胺2 3-二加氧酶1 肿瘤治疗 

分 类 号：R730.3[医药卫生—肿瘤]