Astragaloside IV inhibits metastasis in hepatoma cells through the suppression of epithelial-mesenchymal transition via the Akt/GSK-3 beta/beta-catenin pathway

作者:Qin, Cheng-Dong; Ma, De-Ning; Ren, Zheng-Gang; Zhu, Xiao-Dong; Wang, Cheng-Hao; Wang, Ying-Cong; Ye, Bo-Gen; Cao, Man-Qing; Gao, Dong-Mei; Tang, Zhao-You*
来源:Oncology Reports, 2017, 37(3): 1725-1735.
DOI:10.3892/or.2017.5389

摘要

Our previous studies demonstrated that traditional Chinese herbal medicine `Songyou Yin' inhibited the growth and invasion of hepatocellular carcinoma (HCC) cells, and altered epithelial-mesenchymal transition (EMT) markers in oxaliplatin-treated HCC tissues and cell lines. In the present study, we aimed to explore whether astragaloside IV (AS-IV), a component of `Songyou Yin', can affect the growth and invasion of HCC cells and the underlying mechanism involved. Human HCC cell lines Huh7? and MHCC97-H, with low and high metastatic potential, respectively, were treated with increasing doses of AS-IV. The Cell Counting Kit-8 (CCK-8), plate clone formation, Transwell, wound healing and immunofluorescence assays were used to investigate the effects of AS-IV on HCC cell proliferation, migration and invasion. The protein expression levels were analyzed by western blotting and immunofluorescence assay. The CCK-8 and plate clone formation assays showed that AS-IV had little effect on the proliferation of HCC cells in vitro. However, the Transwell and wound healing assays demonstrated that AS-IV inhibited the migration and invasion of HCC cells in a dose-dependent manner and the morphology of HCC cells was altered from spindle into oval shaped in the AS-IV pretreated groups. The upregulation of E-cadherin and downregulation of N-cadherin, vimentin, alpha-SMA and Slug were also observed in the AS-IV pretreated groups. Additionally, AS-IV treatment resulted in a profound decrease in the phosphorylated forms of Akt and GSK-3 beta, which in turn inhibited the expression of beta-catenin. Thus, we conclude that AS-IV attenuates the invasive and migratory abilities of HCC-cells through the inhibition of EMT by targeting the Akt/GSK-3 beta/beta-catenin pathway.