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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 an iron-containing, flavin-dependent enzyme present in the mitochondrial inner membrane that catalyzes the fourth step of the de novo pyrimidine nucleotide synthesis pathway. Pyrimidine nucleotides can be used for DNA, RNA, glycoprotein and phospholipid biosynthesis, which are crucial for cell metabolism and cell proliferation. Recent studies have shown that DHODH is closely related to the occurrence and development of a variety of tumors. Inhibiting or down-regulating DHODH can reduce tumor cell proliferation, induce apoptosis or increase antitumor effects of other target drugs. Based on the present research results and progress in our laboratory, this paper reviews the related mechanisms of DHODH as a target for the treatment of malignant tumor and the current research progress of DHODH inhibitors.