Transfection of HIF-1 decoy ONDs suppressed expression of VEGF in oral SCC.
Transfection of HIF-1 decoy ONDs suppressed expression of VEGF in oral SCC.
复制标题
HIF-1 诱饵 OND 的转染抑制了口腔 SCC 中 VEGF 的表达。
DOI：
10.1111/j.1600-0714.2012.01161.x
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发表时间：
2012
期刊：
影响因子：
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通讯作者：
et al.
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文献类型：
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作者：
Mie Imai;Hiroaki Ihshibasi;et al.
J Oral Pathol Med(2012)脉管系统发育被认为是实体瘤生长和转移的一个重要方面。在肿瘤细胞产生的众多血管生成因子中，血管内皮生长因子（VEGF）被认为在血管生成过程中发挥着关键作用。 VEGF 的合成受到癌症组织生长的缺氧微环境中缺氧诱导因子 1 (HIF-1) 功能的调节。为了抑制 HIF-1 激活，合成了寡脱氧核苷酸 (ODN)，并将其与 HIF-1 结合的共有序列或该序列的突变形式一起转移。如果我们能够将大量 ODN 转移到癌细胞核中，激活的 HIF-1 可能会与 ODN 结合，从而抑制缺氧诱导的 VEGF 合成。我们使用日本血凝病毒（HVJ）脂质体方法将这些 ODN 转移到培养的口腔鳞状细胞癌细胞（SAS 细胞）中。 HIF-1 诱饵 ODN 转染可抑制癌细胞缺氧介导的 VEGF 表达，但突变的 HIF-1 诱饵 ODN 则不能抑制该表达。 HIF-1诱饵ODN转染也抑制VEGF蛋白合成。这些结果表明，用 HIF-1 诱饵 ODN 转染可通过减少 VEGF 来有效调节肿瘤生长。
J Oral Pathol Med(2012)Vasculature development is thought to be an important aspect in the growth and metastasis of solid tumors. Among the many angiogenic factors produced by tumor cells, vascular endothelial growth factor (VEGF) is considered to play a key role in angiogenic processes. VEGF synthesis is modulated by hypoxia‐inducible factor‐1 (HIF‐1) function within the hypoxic microenvironment of growing cancer tissue. To inhibit HIF‐1 activation, oligodeoxynucleotides (ODNs) were synthesized and transferred with either the consensus sequence for HIF‐1 binding or a mutated form of this sequence. If we could transfer a large number of ODNs into the cancer cell nucleus, activated HIF‐1 might bind to the ODNs, resulting in inhibition of hypoxia‐induced VEGF synthesis. We transferred these ODNs into cultured oral squamous cell carcinoma cells (SAS cells) using thehemagglutinating virus of Japan(HVJ)‐liposome method. Hypoxia‐mediated expression of VEGF by cancer cells was suppressed by transfection of HIF‐1 decoy ODNs, but not by mutated HIF‐1 decoy ODNs. HIF‐1 decoy ODN transfection also inhibited VEGF protein synthesis. These results suggest that transfection with HIF‐1 decoy ODNs is effective for regulating tumor growth by reducing VEGF.