Decursin inhibits the growth of HepG2 hepatocellular carcinoma cells via Hippo/YAP signaling pathway.

Targeted therapy has a pivotal role for the treatment of liver cancer. The aim of this current study was to examine the effects of decursin on the growth of HepG2 cells and the underlying mechanisms. Our present study showed that treatment of HepG2 cells with decursin significantly inhibited the growth of HepG2 cells by suppressing cell proliferation, cell cycle arresting, and promoting apoptosis in a dose- and time-dependent manner. Most significantly, administration of decursin dramatically impeded in vivo tumor growth in nude mice. Mechanically, it is noteworthy that decursin treatment provoked degradation of YAP by upregulating the expression of phosphorylated LATS1 and βTRCP. Moreover, apoptosis caused by decursin could be reversed by a selective MST1/2 inhibitor, XMU-MP-1, suggesting that decursin may function through Hippo/YAP signaling. This study has identified that decursin is a potential agent for HCC therapy, and further research should be undertaken to facilitate its therapeutic application.

Li J ，Wang H ，Wang L ，Tan R ，Zhu M ，Zhong X ，Zhang Y ，Chen B ，Wang L ... -  《-》

Evodiamine inhibits proliferation and promotes apoptosis of hepatocellular carcinoma cells via the Hippo-Yes-Associated Protein signaling pathway.

Dysfunction of the Hippo-Yes-Associated Protein (YAP) signaling pathway is known to be associated with hepatocellular carcinoma (HCC). Evodiamine (Evo), a plant-derived bioactive alkaloid, exerts inhibitory effects on cancer. However, the precise influence of Evo on HCC and its potential effects on Hippo-YAP signaling have yet to be ascertained. Here, the effects of Evo on cell proliferation and apoptosis were evaluated using HCC cell lines (HepG2 and Bel-7402) and nude mice with xenograft tumors. We further investigated whether Evo exerts anti-HCC activity through effects on Hippo-YAP signaling in vitro with the aid of XMU-MP-1, an inhibitor of the key component of this pathway, mammalian sterile 20-like kinase 1/2. Cell proliferation and apoptosis were assessed using 5-ethynyl-2'-deoxyuridine staining, colony formation, flow cytometry, hematoxylin-eosin and dUTP nick-end labeling experiments. Bioinformatics and real-time quantitative polymerase chain reaction (RT-qPCR) arrays were performed to determine the associations among Evo, HCC progression and the Hippo-YAP pathway. The expression patterns of components of Hippo-YAP signaling and apoptotic genes were further examined via RT-qPCR and immunoblotting. Evo inhibited proliferation and promoted apoptosis of HCC cell lines in vitro, and attenuated xenograft tumor formation in nude mice in vivo. Mechanistically, Evo treatment stimulated the Hippo-YAP signaling pathway. In vitro, the effects of Evo on HCC cell proliferation and apoptosis were alleviated by XMU-MP-1. Our collective results revealed that the anti-HCC effects of Evo were correlated with the Hippo-YAP signaling pathway.

Zhao S ，Xu K ，Jiang R ，Li DY ，Guo XX ，Zhou P ，Tang JF ，Li LS ，Zeng D ，Hu L ，Ran JH ，Li J ，Chen DL ... -  《-》

Effect of Mst1 overexpression on the growth of human hepatocellular carcinoma HepG2 cells and the sensitivity to cisplatin in vitro.

Xu C ，Liu C ，Huang W ，Tu S ，Wan F ... -  《-》

TNFAIP8 interacts with LATS1 and promotes aggressiveness through regulation of Hippo pathway in hepatocellular carcinoma.

Dong Q ，Fu L ，Zhao Y ，Xie C ，Li Q ，Wang E ... -  《Oncotarget》

c-Src promotes the growth and tumorigenesis of hepatocellular carcinoma via the Hippo signaling pathway.

We investigated the association between c-Src and the progression of hepatocellular carcinoma (HCC) and its underlying mechanisms. The relationship between c-Src expression and the occurrence and development of HCC was explored using GEPIA and further confirmed by western blotting analysis and real-time quantitative PCR. CCK-8, flow cytometry, Transwell, and wound-healing assays were conducted to analyze the effects of c-Src on the growth, cell cycle, apoptosis, migration, and infiltration of HCC cells. Mouse models of transplanted xenogeneic human tumors were constructed to explore the effects of c-Src on HCC tumor growth. Compared with that in adjacent normal liver tissues, the expression level of c-Src in HCC tissues was significantly increased and was negatively correlated with patient survival. These findings are consistent with those in the GEPIA database. Downregulation of c-Src expression can inhibit the growth, infiltration, and migration of HCC cells. c-Src impeded the translocation of YAP from the nucleus to the cytoplasm and promoted Yes-associated protein transcriptional activity. In vivo experiments showed that c-Src inhibition suppressed tumor growth in mice. We found that c-Src can promote the growth and tumorigenesis of HCC cells by activating the Hippo signaling pathway.

Yang J ，Zhang X ，Liu L ，Yang X ，Qian Q ，Du B ... -  《-》