异柠檬酸脱氢酶1/2突变及其抑制剂在脑胶质瘤中的研究进展
| 作者: |
1,2于佳龙,
3黄南渠,
4施尚鹏,
3巴智胜,
5刘华庆,
2罗勇
1 遵义医学院第三附属医院急诊科，贵州 遵义 563000 2 遵义医学院第三附属医院神经内科，贵州 遵义 563000 3 遵义医学院第三附属医院药物临床试验机构，贵州 遵义 563000 4 遵义医学院第三附属医院科研部，贵州 遵义 563000 5 遵义医学院附属医院病理科，贵州 遵义 563000 |
| 通讯: |
罗勇
Email: 1322869265@qq.com |
| DOI: | 10.3978/j.issn.2095-6959.2018.05.026 |
| 基金: | 基础药理教育部重点实验室暨特色民族药教育部国际合作联合实验室开放课题基金(JCYL-K-012)；贵州省千层次创新型人才[黔市科合人才(2015)25号]；遵义市科学技术局、遵义市第一人民医院联合科技研发资金[遵义市科合社字(2014)27号]。 |
摘要
异柠檬酸脱氢酶(isocitrate dehydrogenase，IDH)是体内具有脱羧作用的氧化还原酶，是三羧酸循环的重要组成部分，在能量代谢中发挥重要作用。IDH1/2突变后能够产生高水平的2-羟基戊二酸(2-hydroxyglutaric，2-HG)，抑制胶质瘤干细胞分化，上调VEGF的表达，促进肿瘤微环境的形成，产生高水平的缺氧诱导因子-1α(hypoxia inducible factor-1α，HIF-1α)促进胶质瘤侵袭，最终导致脑胶质瘤的发生发展。因此针对该靶点的抑制剂和疫苗的研究，将会为脑胶质瘤患者的治疗带来希望。
关键词：
异柠檬酸脱氢酶1/2；脑胶质瘤；抑制剂；疫苗
Research progress of isocitrate dehydrogenase 1/2 mutations and its inhibitor in gliomas
CorrespondingAuthor: LUO Yong Email: 1322869265@qq.com
DOI: 10.3978/j.issn.2095-6959.2018.05.026
Foundation: This work was supported by the Open Funds of Key Laboratory of Basic Pharmacology and Joint International Research Laboratory of Ethnomedicine of Ministry of Education (JCYL-K-012), the Thousand Level of Innovative Talents in Guizhou Province (2015-25)
Abstract
Isocitrate dehydrogenase (IDH) is an oxidoreductase with decarboxylation in vivo. As an important part of the tricarboxylic acid cycle, it plays an important role in energy metabolism. After IDH1/2 mutation, high level of 2-hydroxyglutarate (2-HG) is produced, which inhibits the differentiation of glioma stem cells, upregulates vascular endothelial growth factor (VEGF) to promote the formation of tumor microenvironment, and produces a high level of hypoxia-inducible factor-1α (HIF-1α) to promote glioma invasion, eventually these changes will lead to the development of glioma. Research on the inhibitors and vaccines of IDH1/2 mutations, will give hope to patients with glioma.
Keywords：
isocitrate dehydrogenase 1/2; glioma; inhibitor; vaccine