Liu Jinyi, Zheng Xiangjin, Pang Xiaocong, Li Li, Wang Jinhua, Yang Cui, Du Guanhua
Ethnic Drug Screening & Pharmacology Center, Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission & Ministry of Education, Yunnan Minzu University, Kunming 650500, China.
Key Laboratory of Drug Target Research and Drug Screen, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China.
Acta Pharm Sin B. 2018 Sep;8(5):713-720. doi: 10.1016/j.apsb.2018.07.009. Epub 2018 Jul 25.
Gangliosides are a class of important glycosphingolipids containing sialic acid that are widely distributed on the outer surface of cells and are abundantly distributed in brain tissue. Disialoganglioside with three glycosyl groups (GD3) and disialoganglioside with two glycosyl groups (GD2) are markedly increased in pathological conditions such as cancers and neurodegenerative diseases. GD3 and GD2 were found to play important roles in cancers by mediating cell proliferation, migration, invasion, adhesion, angiogenesis and in preventing immunosuppression of tumors. GD3 synthase (GD3S) is the regulatory enzyme of GD3 and GD2 synthesis, and is important in tumorigenesis and the development of cancers. The study of GD3S as a drug target may be of great significance for the discovery of new drugs for cancer treatment. This review will describe the gangliosides and their roles in physiological and pathological conditions; the roles of GD3 and GD2 in cancers; the expression, functions and mechanisms of GD3S, and its potential as a drug target in cancers.
神经节苷脂是一类含有唾液酸的重要糖鞘脂，广泛分布于细胞外表面，在脑组织中含量丰富。具有三个糖基的双唾液酸神经节苷脂（GD3）和具有两个糖基的双唾液酸神经节苷脂（GD2）在癌症和神经退行性疾病等病理状况下显著增加。研究发现，GD3和GD2通过介导细胞增殖、迁移、侵袭、黏附、血管生成以及防止肿瘤免疫抑制，在癌症中发挥重要作用。GD3合酶（GD3S）是GD3和GD2合成的调节酶，在肿瘤发生和癌症发展中起重要作用。将GD3S作为药物靶点进行研究可能对发现癌症治疗新药具有重要意义。本文综述将描述神经节苷脂及其在生理和病理状况下的作用；GD3和GD2在癌症中的作用；GD3S的表达、功能和机制，以及其作为癌症药物靶点的潜力。
