Apigenin inhibits VEGF and HIF-1 expression via PI3K/AKT/p70S6K1 and HDM2/p53 pathways
Apigenin inhibits VEGF and HIF-1 expression via PI3K/AKT/p70S6K1 and HDM2/p53 pathways
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DOI：
10.1096/fj.04-2175com
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发表时间：
2005-03-01
期刊：
影响因子：
4.8
通讯作者：
Jiang, BH
中科院分区：
文献类型：
--
作者：
Fang, J;Xia, C;Jiang, BH
芹菜素是一种无毒的膳食类黄酮，已被证明具有抗肿瘤特性，因此对开发用于癌症的新型化学预防和/或化学治疗剂具有特别的兴趣。卵巢癌是女性癌症死亡的最常见原因之一。在这里，我们证明芹菜素抑制血管内皮生长因子（VEGF）在人卵巢癌细胞的表达。VEGF在肿瘤血管生成和生长中起重要作用。我们发现，芹菜素通过表达缺氧诱导因子1 α（HIF-1 α）在转录水平抑制VEGF的表达。芹菜素通过PI 3 K/AK-T/p70 S6 K1和HDM 2/ p53途径抑制HIF-1 α和VEGF的表达。芹菜素抑制体外培养的内皮细胞管形成。这些发现揭示了芹菜素在抑制HIF-1和VEGF表达中的新作用，这对肿瘤血管生成和生长很重要，确定了介导这种调节的新信号分子。
Apigenin is a nontoxic dietary flavonoid that has been shown to possess anti-tumor properties and therefore poses special interest for the development of a novel chemopreventive and/or chemotherapeutic agent for cancer. Ovarian cancer is one of the most common causes of cancer death among women. Here we demonstrate that apigenin inhibits expression of vascular endothelial growth factor (VEGF) in human ovarian cancer cells. VEGF plays an important role in tumor angiogenesis and growth. We found that apigenin inhibited VEGF expression at the transcriptional level through expression of hypoxia-inducible factor 1 alpha (HIF-1 alpha). Apigenin inhibited expression of HIF-1 alpha and VEGF via the PI3K/AK-T/p70S6K1 and HDM2/ p53 pathways. Apigenin inhibited tube formation in vitro by endothelial cells. These findings reveal a novel role of apigenin in inhibiting HIF-1 and VEGF expression that is important for tumor angiogenesis and growth, identifying new signaling molecules that mediate this regulation.