Scutellarin suppresses migration and invasion of human hepatocellular carcinoma by inhibiting the STAT3/Girdin/Akt activity

• Published in: Biochemical and biophysical research communications 2017-01, Vol.483 (1), p.509-515
• Main Authors: Ke, Yang, Bao, Tianhao, Wu, Xuesong, Tang, Haoran, Wang, Yan, Ge, Jiayun, Fu, Bimang, Meng, Xu, Chen, Li, Zhang, Cheng, Tan, Yuqi, Chen, Haotian, Guo, Zhitang, Ni, Fan, Lei, Xuefen, Shi, Zhitian, Wei, Dong, Wang, Lin
• Format: Article
• Language: English
• Subjects: Akt; Animals; Antineoplastic Agents, Phytogenic - pharmacology; Apigenin - pharmacology; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - pathology; Cell Movement - drug effects; Cell Proliferation - drug effects; Girdin; Glucuronates - pharmacology; Hep G2 Cells - drug effects; Hep G2 Cells - pathology; Hepatocellular carcinoma; Humans; Invasion; Liver Neoplasms - drug therapy; Liver Neoplasms - pathology; Male; Mice, Inbred BALB C; Microfilament Proteins - antagonists & inhibitors; Microfilament Proteins - metabolism; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Proto-Oncogene Proteins c-akt - metabolism; Scutellarin; STAT3; STAT3 Transcription Factor - antagonists & inhibitors; STAT3 Transcription Factor - metabolism; Vesicular Transport Proteins - antagonists & inhibitors; Vesicular Transport Proteins - metabolism; Xenograft Model Antitumor Assays
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2016.12.114

Scutellarin is an active flavone from Erigeron breviscapine (vant) Hand Mass. This study aimed to investigate the potential role of scutellarin in migration and invasion of human hepatocellular carcinoma (HCC) cells and its possible mechanism. In comparison with the vehicle-treated controls, treatment with scutellarin (50 mg/kg/day) for 35 days significantly mitigated the lung and intrahepatic metastasis of HCC tumors in vivo. Scutellarin treatment significantly reduced HepG2 cell viability in a dose-dependent manner, and inhibited migration and invasion of HCC cells in vitro. Scutellarin treatment significantly reduced STAT3 and Girders of actin filaments (Girdin) expression, STAT3 and Akt phosphorylation in HCC cells. Introduction of STAT3 overexpression restored the scutellarin-downregulated Girdin expression, Akt activation, migration and invasion of HCC cells. Furthermore, induction of Girdin overexpression completely abrogated the inhibition of scutellarin on the Akt phosphorylation, migration and invasion of HCC cells. Scutellarin can inhibit HCC cell metastasis in vivo, and migration and invasion in vitro by down-regulating the STAT3/Girdin/Akt signaling. [Display omitted] •Scutellarin treatment suppresses the lung/intrahepatic metastasis of HCC in vivo.•Scutellarin treatment reduces migration and invasion of HCC cells in vitro.•Scutellarin treatment inhibits the STAT3/Girdin/Akt signaling in HCC cells.•STAT3 overexpression prevents the inhibition of scutellarin in HCC cells.•Girdin overexpression reverses the effects of scutellarin on motility of HCC cells.