Inhibition of hypoxia-induced angiogenesis by FK228, a specific histone deacetylase inhibitor, via suppression of HIF-1α activity
Inhibition of hypoxia-induced angiogenesis by FK228, a specific histone deacetylase inhibitor, via suppression of HIF-1α activity
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DOI：
10.1016/s0006-291x(02)02787-0
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发表时间：
2003-01-03
影响因子：
3.1
通讯作者：
Kim, KW
中科院分区：
文献类型：
--
作者：
Lee, YM;Kim, SH;Kim, KW
缺氧通常在实体瘤的中心区域检测到，并调节包括缺氧诱导因子-1（HIF-1）在内的多种转录因子。HIF-1在细胞对低氧的反应中起着关键作用，如肿瘤的血管生成。在这里，我们发现，历史上的脱乙酰酶（HDAC）抑制剂，FK 228，抑制诱导和缺氧反应的HIF-1的活性。而且。FK 228显著抑制缺氧条件下血管内皮生长因子（VEGF）的诱导。提示FK 228有助于抑制肿瘤血管生成。在刘易斯肺癌模型中，FK 228也能阻断缺氧诱导的血管生成。这些结果表明，FK 228可以通过抑制HIF-1 α活性下调缺氧反应性血管生成。(C)2002 Elsevier Science（美国）。All rights reserved.
Hypoxia is generally detected in central regions of solid tumors and regulates a variety of transcription factors including hypoxia-inducible factor-1 (HIF-1). HIF-1 plays a pivotal role in cellular response to low oxygen concentration, such as angiogenesis in tumor. Here, we found that a historic deacetylase (HDAC) inhibitor, FK228, inhibits the induction and activity of HIF-1 in response to hypoxia. Moreover. FK228 significantly suppressed the induction of vascular endothelial growth factor (VEGF) under hypoxia. suggesting that FK228 contributes to the inhibition of tumor angiogenesis. In Lewis lung carcinoma model, FK228 also blocked angiogenesis induced by hypoxia. These results suggest that FK228 can downregulate hypoxia-responsive angiogenesis through suppression of HIF-1alpha activity. (C) 2002 Elsevier Science (USA). All rights reserved.