Compound Astragalus and Salvia miltiorrhiza extract inhibits cell invasion by modulating transforming growth factor-β/Smad in HepG2 cell

• Published in: Journal of gastroenterology and hepatology 2010-02, Vol.25 (2), p.420-426
• Main Authors: Liu, Xin, Yang, Yan, Zhang, Xiaoxiang, Xu, Shengxin, He, Shufang, Huang, Weijuan, Roberts, Michael S
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents, Phytogenic - pharmacology; Astragalus membranaceus; Biological and medical sciences; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Cell Movement - drug effects; Cell Proliferation - drug effects; compound Astragalus and Salvia miltiorrhiza extract (CASE); Dose-Response Relationship, Drug; Drugs, Chinese Herbal - pharmacology; experimental hepatocarcinogenesis; Gastroenterology. Liver. Pancreas. Abdomen; Hep G2 Cells; hepatocellular carcinoma treatment; HepG2 cells; Humans; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; Neoplasm Invasiveness; Phosphorylation; Plasminogen Activator Inhibitor 1 - genetics; Salvia miltiorrhiza; Signal Transduction - drug effects; Smad; Smad Proteins - metabolism; Transcription, Genetic; Transforming Growth Factor beta1 - metabolism; transforming growth factor-β; Tumors
• ISSN: 0815-9319; 1440-1746
• DOI: 10.1111/j.1440-1746.2009.05981.x

Background and Aims:  Compound Astragalus and Salvia miltiorrhiza extract (CASE) is made up of astragalosides, astragalus polysaccharide and salvianolic acids extracted from Astragalus membranaceus Bunge (Leguminosae) and Salvia miltiorhiza Bunge (Lamiaceae) with a standard ratio. Previous reports showed that CASE inhibited hepatic fibrosis by mediating transforming growth factor (TGF)‐β/Smad signaling. This study further investigated the effect of CASE on hepatoma HepG2 cells stimulated by TGF‐β1 and its potential action mechanisms by TGF‐β/Smad signaling. Methods:  Cell proliferation was studied by MTT assay and cell invasion was evaluated by measuring cell migration through Matrigel. Protein expression in hepatoma HepG2 cells stimulated by TGF‐β1 was analyzed by western blotting and plasminogen activator inhibitor type 1 (PAI‐1) transcriptional activity in HepG2 cells was evaluated. Results:  CASE (40 µg/mL) markedly suppressed cell invasion triggered by TGF‐β1. Smad3 phosphorylation at the linker region (pSmad3L) and Samd2 phosphorylation at the C‐terminal region (pSmad2C) were significantly reduced by CASE. Mild elevated Smad3 phosphorylation at C‐terminal (pSmade3C) region was enhanced by CASE at 20 µg/mL. In addition, treatment of CASE decreased the level of Smad2/3/4 complex at 80 µg/mL, but upregulated the expression of Smad7 in a dose‐dependent manner. CASE also showed inhibitory effect on PAI‐1 transcriptional activity. Conclusion:  All these results suggest that CASE exerts anti‐HepG2 cell invasion effect by modulating TGF‐β/Smad signaling.