Kaempferol inhibits angiogenesis and VEGF expression through both HIF dependent and independent pathways in human ovarian cancer cells.
Kaempferol inhibits angiogenesis and VEGF expression through both HIF dependent and independent pathways in human ovarian cancer cells.
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DOI：
10.1080/01635580802666281
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Chen YC
中科院分区：
文献类型：
--
作者：
Luo H;Rankin GO;Liu L;Daddysman MK;Jiang BH;Chen YC
卵巢癌是西方世界最重要的恶性肿瘤之一，抗血管生成策略已被假定用于预防和治疗卵巢癌。山奈酚是一种天然的类黄酮，存在于许多水果和蔬菜中。在两种卵巢癌细胞系OVCAR-3和A2780/CP 70中研究山奈酚的抗血管生成潜力及其潜在机制。山奈酚轻度抑制细胞活力，但在两种卵巢癌细胞系中显著降低VEGF基因在mRNA和蛋白水平的表达。在鸡胚的绒毛尿囊膜中，山奈酚显著抑制OVCAR-3诱导的血管生成和肿瘤生长。HIF-1α是VEGF的调节因子，在两种卵巢癌细胞系中均被山奈酚处理下调。山奈酚在5至20 μM浓度下也剂量依赖性地抑制AKT磷酸化。ESRRA是一种不依赖HIF的VEGF调节剂，它也以剂量依赖性方式被山奈酚下调。总体而言，这项研究表明，山奈酚是低细胞毒性，但抑制血管生成和VEGF的表达在人卵巢癌细胞通过HIF依赖性（Akt/HIF）和HIF非依赖性（ESRRA）途径，值得进一步研究，在血管预防和治疗卵巢癌的可能应用。
Ovarian cancer is 1 of the most significant malignancies in the Western world, and the antiangiogenesis strategy has been postulated for prevention and treatment of ovarian cancers. Kaempferol is a natural flavonoid present in many fruits and vegetables. The antiangiogenesis potential of kaempferol and its underlying mechanisms were investigated in two ovarian cancer cell lines, OVCAR-3 and A2780/CP70. Kaempferol mildly inhibits cell viability but significantly reduces VEGF gene expression at mRNA and protein levels in both ovarian cancer cell lines. In chorioallantoic membranes of chicken embryos, kaempferol significantly inhibits OVCAR-3-induced angiogenesis and tumor growth. HIF-1α, a regulator of VEGF, is downregulated by kaempferol treatment in both ovarian cancer cell lines. Kaempferol also represses AKT phosphorylation dose dependently at 5 to 20 μM concentrations. ESRRA is a HIF-independent VEGF regulator, and it is also downregulated by kaempferol in a dose-dependent manner. Overall, this study demonstrated that kaempferol is low in cytotoxicity but inhibits angiogenesis and VEGF expression in human ovarian cancer cells through both HIF-dependent (Akt/HIF) and HIF-independent (ESRRA) pathways and deserves further studies for possible application in angio prevention and treatment of ovarian cancers.
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