低氧诱导因子1抑制剂的抗肿瘤研究进展.pdf

·832 · 药学学报 Acta Pharmaceutica Sinica 2014, 49 (6): 832−836 低氧诱导因子 1 抑制剂的抗肿瘤研究进展 , , , * ( 中国医学科学院、北京协和医学院药物研究所, 天然药物活性物质与功能国家重点实验室, 北京 100050) 摘要: 低氧常常发生于急慢性血管疾病和肿瘤形成中。肿瘤细胞适应低氧是由转录因子中的低氧诱导因子 1 (hypoxia-inducible factor 1, HIF-1) 维持的。HIF-1α亚基受氧调控, 决定HIF-1 的活性, 它可引起临床上的治疗耐 受、生长增殖、侵袭转移, 最终导致病人的生存期缩短。因此了解HIF-1 特性及其在信号通路、药物抵抗中的作 用, 是开发新的抗癌疗法的关键。近年来, 针对HIF-1α抑制剂的研究倍受关注。选择性的HIF 抑制剂将为癌症 及与 HIF 相关的疾病提供新的治疗手段。在该篇综述中, 作者将围绕HIF 的生物学特性及作用机制对目前正在 研究的HIF-1 抑制剂加以概述。 关键词: 低氧; 抗肿瘤; HIF-1; HIF-1 抑制剂; 新药开发 中图分类号: R963 文献标识码: A 文章编号: 0513-4870 (2014) 06-0832-05 Research progress of hypoxia-inducible factor 1 inhibitors against tumors * NIU Fei, LI Yan, LAI Fang-fang, CHEN Xiao-guang (State Key Laboratory of Bioactive Substances of Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China) Abstract : Hypoxia occurs in chronic and acute vascular diseases and tumor formation. The ability of tumor cells to maintain a balance between an adaptation to hypoxia and cell death is regulated by a family of transcription factors called hypoxia-inducible factor 1 (HIF-1). Tumor hypoxia mediated by HIF-1 would facilitate the likelihood of resistance to chemotherapy and radiotherapy, proliferation, metastasis and the invasive potential; all of which culminate in a decrease in patient survival. And H