结直肠癌抗代谢药物及其代谢靶点研究进展

Research progress on antimetabolites and related metabolic targets in colorectal cancer

代谢异常在肿瘤的发生、发展中起着至关重要的作用。结直肠癌作为人类最常见的实体肿瘤之一,其代谢异常改变主要涉及有氧糖酵解、谷氨酰胺代谢、脂肪酸代谢以及线粒体代谢等4个方面。针对这些代谢通路中相关转运体、代谢酶为靶点的药物研究逐渐成为研究热点,如冬凌草甲素杀伤细胞的作用靶点是有氧糖酵解通路中的葡萄糖转运体1和单羧酸转运蛋白1,表没食子儿茶素没食子酸酯通过靶向谷氨酰胺代谢通路中谷氨酰胺脱氢酶而诱导细胞凋亡,这些抗代谢药物将在结直肠癌治疗方面发挥巨大的潜力。

Metabolic abnormalities play a crucial role in the occurrence and development of tumors. Colorectal cancer is one of the most common solid tumors in human, and its metabolic abnormalities mainly involved in aerobic glycolysis, glutamine metabolism, fatty acid metabolism and mitochondrial metabolism. Drug research targeting these metabolic pathwayassociated transporters and enzymes has become a research hotspot, such as cells were killed by oridonin by targeting glucose transporter 1 and monocarboxylic acid transporter 1 in the aerobic glycolysis pathway,epigallocatechin gallate induced apoptosis of cells by targeting glutamine dehydrogenase in the glutamine metabolic pathway, and these antimetabolites will have great potential in the treatment of colorectal cancer.