Dihydromyricetin inhibits cell proliferation, migration, invasion and promotes apoptosis via regulating miR-21 in Human Cholangiocarcinoma Cells
Dihydromyricetin inhibits cell proliferation, migration, invasion and promotes apoptosis via regulating miR-21 in Human Cholangiocarcinoma Cells
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二氢杨梅素通过调节人胆管癌细胞中的miR-21抑制细胞增殖、迁移、侵袭并促进细胞凋亡
DOI：
10.7150/jca.45970
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发表时间：
2020-01-01
影响因子：
3.9
通讯作者：
Tan, Sheng-Lan
中科院分区：
文献类型：
--
作者：
Chen, Lei;Yang, Zhou-Sheng;Tan, Sheng-Lan
二氢杨梅素是一种含量最高的天然黄酮类化合物，具有广泛的抗肿瘤作用。然而，二氢杨梅素对胆管癌的作用尚不清楚。本研究考察了二氢杨梅素对人胆管癌细胞HCCC9810和TFK-1的抗肿瘤作用，并对其机制进行了探讨。我们的研究首次发现，二氢杨梅素能显著抑制胆管癌细胞的增殖、迁移、侵袭，促进细胞凋亡。通过分析TCGA数据集，我们发现与配对对照组织相比，胆管癌组织中miR-21的表达上调。miR-21是一种致癌基因，也是胆管癌抗癌药物的潜在靶点。此外，二氢杨梅素以剂量依赖的方式显著降低miR-21的表达。在HCCC9810和TFK-1细胞中，过表达miR-21显著消除了二氢杨梅素对细胞增殖、迁移、侵袭的抑制作用，并消除了其促进细胞凋亡的作用。二氢杨梅素显著增加PTEN的表达，降低磷酸化Akt的表达，而过表达miR-21则取消了二氢杨梅素对PTEN/ Akt通路的调节。综上所述，我们的研究表明，二氢杨梅素通过调节miR-21抑制胆管癌细胞的增殖、迁移、侵袭并促进细胞凋亡。
Dihydromyricetin, the most abundant natural flavonoid isolated from Ampelopsis grossedentata, exhibits broad anti-tumor effects. However, the effects of dihydromyricetin on cholangiocarcinoma remain unclear. This study examined the anti-tumor effects of dihydromyricetin in two human cholangiocarcinoma cell lines HCCC9810 and TFK-1, and the underlying mechanism was also investigated. Our study was the first to show that dihydromyricetin significantly inhibited cell proliferation, migration, invasion and promoted apoptosis in cholangiocarcinoma cells. By analyzing the TCGA dataset, we found that expression of miR-21, an oncogene and a potential target of anticancer drugs for cholangiocarcinoma, was upregulated in cholangiocarcinoma tissues compared to paired control tissues. Moreover, dihydromyricetin significantly reduced the expression of miR-21 in a dose-dependent manner. Overexpression of miR-21 remarkably abolished the inhibitory effects of dihydromyricetin on cell proliferation, migration, invasion and abrogated its effect of promoting cell apoptosis in both HCCC9810 and TFK-1 cells. Dihydromyricetin remarkably increased the expression of PTEN and decreased the expression of phosphorylated Akt, while overexpression of miR-21 abrogated the modulation of PTEN/ Akt pathway by dihydromyricetin. Taken together, our study demonstrates that dihydromyricetin inhibits cell proliferation, migration, invasion and promotes apoptosis in cholangiocarcinoma cells via regulating miR-21.