Genipin inhibits the invasion and migration of colon cancer cells by the suppression of HIF-1α accumulation and VEGF expression
Genipin inhibits the invasion and migration of colon cancer cells by the suppression of HIF-1α accumulation and VEGF expression
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DOI：
10.1016/j.fct.2018.04.005
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发表时间：
2018-06-01
影响因子：
4.3
通讯作者：
Lee, Dae-Hee
中科院分区：
文献类型：
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作者：
Lee, Suk-young;Kim, Hong Jun;Lee, Dae-Hee
缺氧诱导因子-1 (HIF-1) 和血管内皮生长因子 (VEGF) 在各种癌细胞系的癌症进展中发挥着重要作用。尽管栀子果实的成分京尼平已被证明具有抗肿瘤活性，但其在抑制 HIF-1 及其下游靶基因中的作用尚不清楚。我们使用结肠癌细胞系 HCT116 检查了京尼平对细胞内 HIF-1α 水平和细胞外 VEGF 水平的影响。我们观察到，京尼平通过调节蛋白质降解，抑制了包括 HCT116 在内的多种癌细胞系在缺氧条件下 HIF-1 α 的积累。京尼平还通过阻断细胞外信号调节激酶信号通路来抑制 VEGF 的表达和结肠癌细胞的侵袭。总而言之，我们的结果为京尼平在抑制结肠癌进展中的潜在作用提供了新的见解。
Hypoxia-inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) play important roles in cancer progression in various cancer cell lines. Although genipin, a constituent of Gardenia fruit, has been shown to have anti-tumor activity, its role in the suppression of HIF-1 and its downstream target genes is not well understood. We examined the effect of genipin on the intracellular level of HIF-la and extracellular level of VEGF using the colon cancer cell line HCT116. We observed that genipin suppressed the accumulation of HIF-1 alpha under hypoxia in various cancer cell lines, including HCT116, via the modulation of protein degradation. Genipin also suppressed the expression of VEGF and the invasion of colon cancer cells by blocking the extracellular signal-regulated kinase signaling pathway. Taken together, our results provide new insights into the potential role of genipin in suppressing colon cancer progression.