Artemisinin suppresses hepatocellular carcinoma cell growth, migration and invasion by targeting cellular bioenergetics and Hippo-YAP signaling
Artemisinin suppresses hepatocellular carcinoma cell growth, migration and invasion by targeting cellular bioenergetics and Hippo-YAP signaling
复制标题
青蒿素通过靶向细胞生物能学和 Hippo-YAP 信号传导来抑制肝细胞癌细胞的生长、迁移和侵袭。
DOI：
10.1007/s00204-019-02579-3
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发表时间：
2019-11-01
影响因子：
6.1
通讯作者：
Lu, Bin
中科院分区：
文献类型：
--
作者：
Li, Yujie;Lu, Jing;Lu, Bin
原发性肝癌（PLC）是全球癌症相关死亡的主要原因之一。原发性肝癌（hepatocellular carcinoma，HCC）是原发性肝癌的主要类型，约占所有原发性肝癌的85%。青蒿素（Artemisinin，ART）是临床上常用的抗疟药。最近，它被证明在多种癌症类型中抑制细胞生长和迁移。然而，这些抗癌活性背后的分子机制在很大程度上仍然未知。在此，发现ART通过阻滞细胞周期进程在体外显著抑制HCC细胞生长，并且通过调节N-cadherin-Snail-E-cadherin轴抑制细胞迁移和侵袭。此外，细胞生物能量学的破坏有助于ART引起的细胞生长、迁移和侵袭抑制。此外，ART（100 mg/kg，腹膜内）在体内基本上抑制HCC异种移植物生长。重要的是，Hippo-YAP信号转导在ART施用后在HCC细胞中显著失活。这些数据揭示了ART调节HCC细胞生长、迁移和侵袭的新机制，表明ART可能被认为是治疗HCC的潜在药物。
The primary liver cancer (PLC) is one of the leading causes of cancer-related death worldwide. The predominant form of PLC is hepatocellular carcinoma (HCC), which accounts for about 85% of all PLC. Artemisinin (ART) was clinically used as anti-malarial agents. Recently, it was demonstrated to inhibit cell growth and migration in multiple cancer types. However, the molecular mechanism underlying these anti-cancer activity remains largely unknown. Herein, it is discovered that ART dramatically suppresses HCC cell growth in vitro through arresting cell cycle progression, and represses cell migration and invasion via regulating N-cadherin-Snail-E-cadherin axis. In addition, the disruption of cellular bioenergetics contributed to ART-caused cell growth, migration and invasion inhibition. Moreover, ART (100 mg/kg, intraperitoneally) substantially inhibits HCC xenograft growth in vivo. Importantly, Hippo-YAP signal transduction is remarkably inactivated in HCC cells upon ART administration. Collectively, these data reveal a novel mechanism of ART in regulating HCC cell growth, migration, and invasion, which indicates that ART could be considered as a potential drug for the treatment of HCC.