Actinidia chinensis Planch root extract (acRoots) inhibits hepatocellular carcinoma progression by inhibiting EP3 expression
Actinidia chinensis Planch root extract (acRoots) inhibits hepatocellular carcinoma progression by inhibiting EP3 expression
复制标题
中华猕猴桃根提取物 (acRoots) 通过抑制 EP3 表达来抑制肝细胞癌进展。
DOI：
10.1007/s10565-016-9351-z
复制
发表时间：
2016-12-01
影响因子：
6.1
通讯作者：
Xia, Jinglin
中科院分区：
文献类型：
--
作者：
Fang, Tingting;Hou, Jiayun;Xia, Jinglin
广泛的研究已经证明中草药具有强大的抗癌活性。在这里，我们评估了猕猴桃根提取物（acRoots）对肝细胞癌（HCC）的抗癌活性和分子机制。 HepG2 HCC 细胞用不同浓度的 acRoots 处理 72 小时，并通过 mRNA 表达谱进行检查，揭示细胞免疫、炎症、增殖、细胞周期和代谢信号反应的变化。对细胞免疫和炎症基因簇中改变的基因的进一步分析发现，前列腺素 E 受体 3 (EP3) 是响应 acRoots 的基因表达的关键调节因子。进一步的分析显示，acRoots 可抑制 HCC 中的细胞生长、迁移和侵袭，并且由于 EP3 表达下调而导致细胞凋亡增加。 acRoots 和 EP3 拮抗剂 L-798106 治疗可导致 HCC 细胞中 VEGF、EGFR、MMP2 和 MMP9 表达降低，并对生长、迁移、侵袭和凋亡产生显着影响； EP3 激动剂磺前列酮可逆转/阻断该作用。总而言之，这些数据清楚地表明，acRoots 通过抑制 EP3 表达来抑制 HCC 细胞侵袭和转移，从而导致 VEGF、EGFR、MMP2 和 MMP9 的激活减少。
A wide range of studies has demonstrated the potent anticancer activity of Chinese herbs. Here, we evaluated the anticancer activity and molecular mechanisms of Actinidia chinensis root extract (acRoots) on hepatocellular carcinoma (HCC). HepG2 HCC cells were treated with various concentrations of acRoots for 72 h and examined by mRNA expression profiling, revealing alterations in cellular immunity, inflammation, proliferation, cell cycle, and metabolic signaling responses. Further analysis of the altered genes in cellular immunity and inflammation gene clusters identified prostaglandin E receptor 3 (EP3) as a key regulator of gene expression in response to acRoots. Further analysis revealed inhibition of cell growth, migration, and invasion in HCC in response to acRoots, along with increased apoptosis due to downregulation of EP3 expression. Treatment with acRoots and EP3 antagonist L-798106 led to decreases in VEGF, EGFR, MMP2, and MMP9 expression in HCC cells, along with significant effects on growth, migration, invasion, and apoptosis; the effects were reversed/blocked by the EP3 agonist sulprostone. Taken together, these data clearly demonstrated that acRoots inhibit HCC cell invasion and metastasis via inhibition of EP3 expression, resulting in decreased activation of VEGF, EGFR, MMP2, and MMP9.