CDDO及其衍生物抗肿瘤作用及机制的研究进展  

Research progress of anti-tumor effect and mechanism of CDDO and its derivatives

作　　者：王梦莹 张欣禹 杜盼 陈丽艳 WANG Mengying;ZHANG Xinyu;DU Pan;CHEN Liyan(Tumor Research Center of Yanbian University Medical College,Jilin Yanji 133002,China;Key Laboratory of Pathobiology of High Frequency Oncology in Ethnic Minority Areas(Yanbian University),State Ethnic Affairs Commission,Jilin Yanji 133002,China)

机构地区：[1]延边大学医学院肿瘤研究中心,吉林延吉133002 [2]民族地区高发肿瘤病理生物学国家民委重点实验室(延边大学),吉林延吉133002

出　　处：《中国药房》2023年第18期2287-2292,共6页China Pharmacy

基　　金：国家自然科学基金项目(No.82160695)。

摘　　要：2-氰基-3,12-二氧代齐墩果烷-1,9(11)-二烯-28-羧酸(CDDO)是以天然三萜类化合物齐墩果酸为先导物或前体,将分子中3个可修饰的官能团经过一系列化学结构改造合成的一种化合物;为了提高其抗肿瘤活性,又进一步合成了CDDO衍生物。本文归纳总结了近年来CDDO及其衍生物抗肿瘤作用及机制的研究成果,发现CDDO及其衍生物具有广泛的抗肿瘤作用,能够在微摩尔甚至纳摩尔等较低浓度下对乳腺癌、胰腺癌、肺癌和卵巢癌等表现出显著的抗肿瘤作用,其中CDDO甲酯化合物(CDDOMe)和CDDO咪唑啉酮化合物(CDDO-Im)作用效果最为明显;CDDO及其衍生物主要通过诱导肿瘤细胞凋亡、调控代谢重编程及免疫微环境等发挥抗肿瘤活性,其涉及通路主要包括Janus蛋白酪氨酸激酶(JAK)/信号传导及转录激活蛋白3(STAT3)信号通路、核因子E2相关因子2(NRF2)信号通路、磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(又称Akt)/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路、Wnt/β-连环蛋白(β-catenin)信号通路和核因子κB信号通路等。2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid(CDDO)is a compound synthesized by taking oleanolic acid,a natural triterpene,as a precursor or precursor,and transforming three modifiable functional groups in the molecule through a series of chemical structure modification.In order to improve its anti-tumor activity,CDDO derivatives are further synthesized.In this paper,the research results of anti-tumor effects and mechanisms of CDDO and its derivatives in recent years are summarized.It is found that CDDO and its derivatives have a wide range of anti-tumor effects,and can show significant anti-tumor effects on breast cancer,pancreatic cancer,lung cancer and ovarian cancer at low concentrations such as micromole or even nanomole,among which CDDO methyl ester compound(CDDO-Me)and CDDO imidazolidinone compound(CDDO-Im)have the most obvious effects.CDDO and its derivatives exert anti-tumor activity mainly by inducing tumor cell apoptosis,and regulating metabolic reprogramming and immune microenvironment.The involved pathways mainly include Janus protein tyrosine kinase(JAK)/signal transduction and transcription activation protein 3(STAT3)signal pathway,nuclear factor E2-related factor 2(NRF2)signal pathway,phosphatidylinositol 3 kinase(PI3K)/protein kinase B(also known as Akt)/mammalian rapamycin target protein(mTOR)signal pathway,Wnt/β-catenin signal pathway,nuclear factorκB signal pathway.

关 键 词：2-氰基-3 12-二氧代齐墩果烷-1 9(11)-二烯-28-羧酸 衍生物 抗肿瘤活性 作用机制 

分 类 号：R965[医药卫生—药理学]