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

Abstract

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, α-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-3β, which in turn inhibited the expression of β-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-3β/β-catenin pathway.

Ginsenoside Rg1 Alleviates Podocyte EMT Passage by Regulating AKT/GSK3 β/β‐Catenin Pathway by Restoring Autophagic Activity

“…β-catenin eventually enters the nucleus and triggers EMT [44]. Astragaloside IV inhibits EMT by targeting the AKT/ GSK3β/β-catenin pathway, which weakens the invasion and migration of hepatocellular carcinoma cells [45]. Autophagy is an important part of cellular activity; however, its relationship with the AKT/GSK3β/β-catenin pathway is still unclear.…”

Effect of astragaloside IV and the role of nuclear receptor RXRα in human peritoneal mesothelial cells in high glucose‑based peritoneal dialysis fluids

“…Astragaloside IV inhibits cell viability, invasion, migration and TGF-β1-induced EMT in gastric cancer cells through inhibition of the PI3K/AKT/NF-κB pathway (68). Astragaloside IV inhibits the invasion and migration of hepatocellular carcinoma cells by reducing EMT via effect on the AKT/glycogen synthase kinase-3β/β-catenin pathway (69), and suppressing long noncoding RNA activated by TGF-β/interleukin-11/STAT3 signaling (70). Therefore, it is speculated that similar signaling pathways may also be involved in the protective effects of astragaloside IV in PMCs to prevent damage from high glucose-based PD fluids, in addition to the upregulation of Smad7 in the TGF-β1/Smad signaling pathway during the inhibition of TGF-β1-induced PMC EMT by astragaloside IV (31).…”

Astragaloside IV inhibits TGF‐β1‐induced epithelial‐mesenchymal transition through inhibition of the PI3K/Akt/NF‐κB pathway in gastric cancer cells

“…Recently, some agents were found to suppress GC EMT, which shed light on its antitumor effects (He et al, ). It was reported that AS‐IV inhibited metastasis in hepatoma cells through the suppression of EMT (Qin et al, ). However, whether AS‐IV could suppress EMT of cancer cells was rarely reported.…”