Compound Astragalus and Salvia miltiorrhiza extract inhibits cell invasion by modulating transforming growth factor-beta/Smad in HepG2 cell.
OBJECTIVE
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)-beta/Smad signaling. This study further investigated the effect of CASE on hepatoma HepG2 cells stimulated by TGF-beta(1) and its potential action mechanisms by TGF-beta/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-beta(1) was analyzed by western blotting and plasminogen activator inhibitor type 1 (PAI-1) transcriptional activity in HepG2 cells was evaluated.


RESULTS
CASE (40 microg/mL) markedly suppressed cell invasion triggered by TGF-beta(1). 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 microg/mL. In addition, treatment of CASE decreased the level of Smad2/3/4 complex at 80 microg/mL, but upregulated the expression of Smad7 in a dose-dependent manner. CASE also showed inhibitory effect on PAI-1 transcriptional activity.


CONCLUSIONS
All these results suggest that CASE exerts anti-HepG2 cell invasion effect by modulating TGF-beta/Smad signaling.
Liu
Xin
X
Department of Pharmacology, Anhui Medical University, Hefei, Anhui, China.
Yang
Yan
Y
Zhang
Xiaoxiang
X
Xu
Shengxin
S
He
Shufang
S
Huang
Weijuan
W
Roberts
Michael S
MS
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D027885:Astragalus propinquus; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D027561:Salvia miltiorrhiza; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000378:metabolism*; D014158:Transcription, Genetic; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1