二氢乳清酸脱氢酶作为抗肿瘤靶点的研究进展

Advances in DHODH:A Target for Treating Tumors

二氢乳清酸脱氢酶(dihydroorotate dehydrogenase,DHODH)是存在于线粒体内膜的一种含铁的黄素依赖酶,这种酶催化嘧啶核苷酸从头合成途径的第4步反应。而嘧啶核苷酸可用于DNA、RNA、糖蛋白和磷脂生物合成,对于细胞代谢和细胞增殖至关重要。近年来的研究表明,DHODH与多种肿瘤的发生、发展密切相关,抑制或下调DHODH可以降低肿瘤细胞增殖,诱导其凋亡或者增加其他靶点药物的抗肿瘤效果。该文结合所在实验室目前的研究成果及进展,就DHODH作为治疗恶性肿瘤靶点的相关机制及当前DHODH抑制剂的研究进展作一综述。

Dihydroorotate dehydrogenase （DHODH） is the fourth enzyme of pyrimidine nucleotide de novo synthesis that catalyzes the conversion of dihydroorotate to orotate. Pyrimidine bases are essential for cellular metabolism and cell proliferation, and are considered as important precursors used in the biosynthesis of DNA, RNA, glycoproteins and phospholipids. In recent years, more and more studies confirmed that the expression of DHODH gene was associated with the development of a variety of tumors. Therefore, DHODH had some research prospects as a new anticancer target. Based on research achievements and advances of our laboratory, we depicted the related mechanisms of DHODH in cancer treatment and the research progress of DHODH inhibitors in this review.