Acacetin inhibits VEGF expression, tumor angiogenesis and growth through AKT/HIF-1α pathway.
Acacetin inhibits VEGF expression, tumor angiogenesis and growth through AKT/HIF-1α pathway.
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DOI：
10.1016/j.bbrc.2011.08.091
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发表时间：
2011-09-23
影响因子：
3.1
通讯作者：
Jiang, Bing-Hua
中科院分区：
文献类型：
--
作者：
Liu, Ling-Zhi;Jing, Yi;Jiang, Lisa L.;Jiang, Xiu-E;Jiang, Yue;Rojanasakul, Yongyut;Jiang, Bing-Hua
金合欢素（5，7-二羟基-4 ′-甲氧基黄酮）是一种黄酮类化合物，其中一些化合物具有抗癌作用。血管内皮生长因子（VEGF）在血管生成和肿瘤生长中起重要作用。在本研究中，我们发现金合欢素降低了VEGF mRNA水平的稳定水平，抑制了VEGF的转录激活。为了进一步确定金合欢素抑制VEGF表达的潜在机制，我们发现金合欢素抑制HIF-1α表达和AKT活化。HIF-1α或AKT的过表达恢复了金合欢素降低的VEGF转录激活，表明AKT和HIF-1是金合欢素抑制细胞中VEGF表达的重要下游靶点。此外，金合欢素通过抑制HIF-1α和VEGF的表达，显著抑制卵巢癌细胞诱导的血管生成和肿瘤生长。金合欢素不影响HIF-1α mRNA水平，但通过增加其降解和降低其稳定性抑制HIF-1α蛋白水平。这些结果表明，金合欢素可能是一个有用的天然化合物，用于卵巢癌的预防和治疗。
Acacetin (5,7-dihydroxy-4′-methoxyflavone) is a flavone compound, some of which have anti-cancerous effects. Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis and tumor growth. In this study, we found that acacetin decreased the steady level of VEGF mRNA level and inhibited VEGF transcriptional activation. To further determine the potential mechanism of acacetin in inhibiting VEGF expression, we showed that acacetin inhibited HIF-1α expression and AKT activation. Over-expression of HIF-1α or AKT restored acacetin-decreasing VEGF transcriptional activation, indicating that AKT and HIF-1 are the essential downstream targets of acacetin for inhibiting VEGF expression in the cells. Moreover, acacetin significantly inhibited ovarian cancer cell-induced angiogenesis and tumor growth in vivo through inhibiting HIF-1α and VEGF expression. Acacetin did not change HIF-1α mRNA level, but inhibited HIF-1α protein level through increasing its degradation and decreasing its stability. These results indicate that acacetin may be a useful natural compound for ovarian cancer prevention and treatment.
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影响因子：
5.6
作者：
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通讯作者：
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影响因子：
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作者：
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