摘要
缺氧是包括肿瘤在内的许多疾病的重要特征,利用缺氧条件来选择性抑制肿瘤生长和演进是一个很有前途的研究方向。随着缺氧诱导因子-1(HIF-1)的发现,过去15年里在分子和细胞水平上对缺氧有了更加深刻的认识,HIF-1是真核细胞在缺氧条件下进行代谢调控的关键因子,控制众多基因的表达,影响氧的转运、糖摄取、糖酵解和血管生成等。下调HIF-1水平可以作为肿瘤治疗手段。由于细胞内对HIF-1的调控主要通过其α亚基进行,因此HIF-1α抑制剂成为抗肿瘤药物的研究热点。已经发现的该类抑制剂包括喜树碱类、喹啉类、雷帕霉素类、一些甾体化合物、苯氧乙酰氨基苯甲酸类以及白藜芦醇和橙皮苷等天然产物。本文就HIF-1α的结构、功能和以其为靶点的抗肿瘤药物的研究进展做一综述。
Hypoxia is an important characteristic of neoplasma and some other diseases. For this reason, it is becoming an attractive research area to inhibit tumor growth by utilizing the hypoxia environment. The discovery of hypoxia inducible factor-1 （ HIF-1 ） has led to a rapidly increasing understanding of the molecular mechanism of tumor hypoxia in the past 15 years. Now it is generally accepted that HIF-1 performs a central role for tumor cells to regulate their metabolisms under hypoxia. Many genes are regulated by HIF-1, their expression will affect oxygen transportation, glucose uptake, glucolysis, and angiogenesis. Therefore, down regulation of the HIF system may interfere tumor＇s adaption to hypoxia, thus making it an attractive target for cancer therapy. As most regulations occur on the HIF-la subunit, researches focus on targeting HIF-1α, which lead to the discovery of a variety of small molecular HIF-1α inhibitors including camptothecin analogues, quinoxaline analogues, rapamycin analogues, some steroids, （aryloxyacetylamino） benzoic acid analogues and some naturally occurring substances like resveratrol and hesperidin. Here we summarize recent information on HIF-1α, especially HIF-1α inhibitors that have the potential of clinical usage.
出处
《化学进展》
SCIE
CAS
CSCD
北大核心
2008年第12期2068-2074,共7页
Progress in Chemistry
基金
江苏省自然科学基金项目(No.BK2007168)资助
关键词
缺氧诱导因子-1Α
肿瘤
抑制剂
hypoxia inducible factor-1α（HIF-1α）
cancer
inhibitors
