药学学报, 2021, 56(10): 2689-2719
引用本文:
史新萌, 刘玉萍, 瞿鼎, 黄琳清, 陈彦. 抑制HIF-1α表达的中药抗肿瘤活性成分研究进展[J]. 药学学报, 2021, 56(10): 2689-2719.
SHI Xin-meng, LIU Yu-ping, QU Ding, HUANG Lin-qing, CHEN Yan. Research progress of anti-tumor components of traditional Chinese medicine inhibiting the expression of HIF-1α[J]. Acta Pharmaceutica Sinica, 2021, 56(10): 2689-2719.

抑制HIF-1α表达的中药抗肿瘤活性成分研究进展
史新萌1,2, 刘玉萍1,2, 瞿鼎1,2, 黄琳清1,2, 陈彦1,2*
1. 南京中医药大学附属中西医结合医院, 江苏 南京 210028;
2. 江苏省中医药研究院, 中药组分与微生态研究中心, 江苏 南京 210028
摘要:
实体肿瘤的重要特征之一是缺氧,缺氧微环境可导致缺氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)的过度表达。HIF-1α是缺氧应答中最为关键的转录因子,可通过激活下游基因表达促进肿瘤细胞异常增殖、肿瘤血管生成、能量代谢异常、耐药性增加、侵袭和转移。因此,下调HIF-1α的表达是一条目前被认为治疗实体肿瘤的很有前景的途径。然而,大多数现有的HIF-1α抑制剂的临床效果受到低效性和高毒性的限制。由此,针对HIF-1α的过度表达研发强效安全的新型药物尤为重要。近年来,大量研究发现多种中药化学成分可直接或间接抑制HIF-1α的激活,在对抗低氧诱导的肿瘤进展过程方面具有广阔的前景。本综述汇总了近十年内直接或间接抑制HIF-1α表达的各种中药抗肿瘤活性成分的研究进展,并进行总结与讨论,以期为进一步研究作为参考。
关键词:    缺氧诱导因子-1α      中药      肿瘤      缺氧      机制     
Research progress of anti-tumor components of traditional Chinese medicine inhibiting the expression of HIF-1α
SHI Xin-meng1,2, LIU Yu-ping1,2, QU Ding1,2, HUANG Lin-qing1,2, CHEN Yan1,2*
1. Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China;
2. Multi-component of Traditional Chinese Medicine and Microecology Research Center, Jiangsu Provincial Academy of Chinese Medicine, Nanjing 210028, China
Abstract:
Hypoxia is one of the most significant characteristics of solid tumors. Hypoxia microenvironment can lead to the overexpression of hypoxia inducible factor-1α (HIF-1α). As the most critical transcription factor in the hypoxia response, HIF-1α activates downstream gene expression resulting in abnormal tumor cell proliferation, tumor angiogenesis, unusual energy metabolism, increased drug resistance, invasion, and metastasis. Down-regulation of HIF-1α expression is considered as a promising approach for the treatment of solid tumors, whereas the clinical efficacy of most existing HIF-1α inhibitors is restricted in low efficacy and high toxicity. Therefore, it is particularly important to develop powerful and safe novel drugs against the overexpression of HIF-1α. In recent years, numbers of studies have proved that a variety of chemical components of traditional Chinese medicine can directly or indirectly inhibit the activation of HIF-1α, which has a broad prospect in the fight against hypoxia-induced tumor progression. In this review, we summarized various anti-tumor active components of traditional Chinese medicines responsible for inhibiting the expression of HIF-1α in last ten years and analyzed the corresponding mechanism, with a view to further research as a reference.
Key words:    hypoxia inducible factor-1α    traditional Chinese medicine    tumor    hypoxia    mechanism   
收稿日期: 2021-01-28
DOI: 10.16438/j.0513-4870.2021-0167
基金项目: 江苏省卫生健康委医学科研项目(K2019007);江苏省科教强卫医学重点人才项目(ZDRCA2016036).
通讯作者: 陈彦,Tel:86-25-85608672,E-mail:ychen202@hotmail.com
Email: ychen202@hotmail.com
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