姜黄素通过抑制 STAT3 和 PI3K/AKT 抑制肝癌细胞的血管生成拟态能力。
Curcumin suppresses vasculogenic mimicry capacity of hepatocellular carcinoma cells through STAT3 and PI3K/AKT inhibition.
机构信息
Laboratory of Biochemistry, Chulabhorn Research Institute, 54 Kamphaeng Phet 6, Talat Bang Khen, Laksi, Bangkok 10210, Thailand.
出版信息
Anticancer Res. 2014 Apr;34(4):1857-64.
BACKGROUND
Vasculogenic mimicry (VM) refers to the process in which highly invasive cancer cells mimic endothelial cells by forming blood channels. In the present study, we investigated the effect of curcumin, a natural product from turmeric, on VM of SK-Hep-1 human hepatocellular carcinoma (HCC) cells.
MATERIALS AND METHODS
In vitro VM, cell migration, and matrix metalloproteinase-9 (MMP9) production of HCC cells were determined by Matrigel tube formation assay, Transwell cell migration assay, and gelatin zymography, respectively. Effects of curcumin on AKT, signal transducer and activator of transcription 3 (STAT3), extracellular signal-regulated kinase (ERK) and nuclear factor-κB (NF-κB) signaling pathways were determined by immunoblot analysis.
RESULTS
At non-cytotoxic concentrations, curcumin inhibited VM, reduced cell migration and MMP9 production of the HCC cells. Further study revealed that the anti-VM effect of curcumin was due to inhibition of AKT and STAT3 phosphorylation, as confirmed by specific inhibitors.
CONCLUSION
Curcumin presents proven potential as an anti-VM agent in HCC cells, through down-regulation of STAT3 and AKT signaling pathways.
背景
血管生成拟态（VM）是指高度侵袭性癌细胞通过形成血管来模拟内皮细胞的过程。在本研究中，我们研究了姜黄素（一种来自姜黄的天然产物）对 SK-Hep-1 人肝癌（HCC）细胞 VM 的影响。
材料与方法
通过 Matrigel 管形成测定、Transwell 细胞迁移测定和明胶酶谱法分别测定 HCC 细胞的体外 VM、细胞迁移和基质金属蛋白酶-9（MMP9）的产生。通过免疫印迹分析测定姜黄素对 AKT、信号转导和转录激活因子 3（STAT3）、细胞外信号调节激酶（ERK）和核因子-κB（NF-κB）信号通路的影响。
结果
在非细胞毒性浓度下，姜黄素抑制了 HCC 细胞的 VM、减少了细胞迁移和 MMP9 的产生。进一步的研究表明，姜黄素的抗 VM 作用是由于 AKT 和 STAT3 磷酸化的抑制，这一点通过特异性抑制剂得到了证实。
结论
姜黄素通过下调 STAT3 和 AKT 信号通路，为 HCC 细胞提供了一种有效的抗 VM 药物。
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