低氧诱导因子及其抑制剂研究进展  

Progress on Hypoxia-inducible Factor and its Inhibitors

作　　者：闫东科 吕平[1] YAN Dongke;LYU Ping(Department of Food Biotechnology, School of Biological and Environmental Engineering, Tianjin Vocational Institute, Tianjin 300350, China)

机构地区：[1]天津职业大学生物与环境工程学院食品生物技术系

出　　处：《生物技术进展》2019年第4期332-340,共9页Current Biotechnology

摘　　要：低氧(hypoxia)是生物体内常见的生理和病理现象,也是常见的实体肿瘤微环境。人和其他哺乳动物体内存在一系列应对缺氧胁迫的调节机制,而低氧诱导因子(hypoxia-inducible factors,HIFs)是这些调节机制中的关键调控因子,是一类参与细胞缺氧应答反应的转录因子家族。大量研究表明,HIFs与生物体的生长、发育、血管生成、红细胞生成、细胞代谢和自噬以及肿瘤的发生、发展、转移侵袭、放化疗抗性和癌症患者的不良预后等密切相关。因此,进一步加强HIFs及其抑制剂的相关研究对于肿瘤的认识与治疗具有重要意义。从HIFs的蛋白质结构、稳定性调控、转录激活调控及其靶向抑制剂的研究进展等方面进行综述,以期为靶向HIFs的肿瘤治疗提供新线索,为新型HIFs抑制剂的研究与开发提供参考。Hypoxia is a common physiological and pathological phenomenon in vivo and a common microenvironment of solid tumors. There are a series of regulation mechanisms in humans and other mammals to deal with hypoxia stress. And hypoxia-inducible factors(HIFs) are the key regulators of these regulation mechanisms, and they are a family of transcription factors involved in cellular hypoxia response. Extensive studies have shown that HIFs are closely related to growth and development of organisms, angiogenesis, erythropoiesis, cell metabolism and autophagy, and occurrence, development, metastasis and invasion, radiochemotherapy resistance of tumor as well as poor prognosis of cancer patients. Therefore, it is of great significance to further strengthen the research on HIFs and their inhibitors for the understanding and treatment of tumors. The progress of protein structure, stability regulation, transcriptional activation regulation and targeted inhibitors of HIFs was reviewed, in order to provide new insights in HIFs targeted tumor therapy and offer references for the research and development of new HIFs inhibitors.

关 键 词：低氧诱导因子 稳定性调控 转录活性 靶向抑制剂 肿瘤治疗 

分 类 号：R914[医药卫生—药物化学]