抑制HIF-1α表达的中药抗肿瘤活性成分研究进展

Research progress of anti-tumor components of traditional Chinese medicine inhibiting the expression of HIF-1α

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。

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-1αactivates downstream gene expression resulting in abnormal tumor cell proliferation,tumor angiogenesis,unusual energy metabolism,increased drug resistance,invasion,and metastasis.Down-regulation of HIF-1αexpression is considered as a promising approach for the treatment of solid tumors,whereas the clinical efficacy of most existing HIF-1αinhibitors 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-1αin last ten years and analyzed the corresponding mechanism,with a view to further research as a reference.