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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
硕士研究生。研究方向:肿瘤分子生物学。E-mail:wangmengying0216@163.com
教授,博士生导师,博士。研究方向:肿瘤分子生物学。E-mail:lychen@ybu.edu.cn
收稿日期:2023-04-03,
修回日期:2023-08-15,
录用日期:2023-08-23,
纸质出版日期:2023-09-30
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王梦莹,张欣禹,杜盼,等.CDDO及其衍生物抗肿瘤作用及机制的研究进展[J].中国药房,2023,34(18):2287-2292.
WANG Mengying,ZHANG Xinyu,DU Pan,et al.Research progress of anti-tumor effect and mechanism of CDDO and its derivatives[J].ZHONGGUO YAOFANG,2023,34(18):2287-2292.
王梦莹,张欣禹,杜盼,等.CDDO及其衍生物抗肿瘤作用及机制的研究进展[J].中国药房,2023,34(18):2287-2292. DOI: 10.6039/j.issn.1001-0408.2023.18.21.
WANG Mengying,ZHANG Xinyu,DU Pan,et al.Research progress of anti-tumor effect and mechanism of CDDO and its derivatives[J].ZHONGGUO YAOFANG,2023,34(18):2287-2292. DOI: 10.6039/j.issn.1001-0408.2023.18.21.
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(CDDO-Me)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 synth
esized. 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 factor κB signal pathway.
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