Stachydrine inhibits TGF-β1-induced epithelial-mesenchymal transition in hepatocellular carcinoma cells through the TGF-β/Smad and PI3K/Akt/mTOR signaling pathways

Stachydrine is a bioactive alkaloid that has been found to exert tumor-suppressive potential. However, the effect of stachydrine on hepatocellular carcinoma (HCC) has not been previously investigated. In the present study, we investigated the effect of transforming growth factor-beta 1 (TGF-beta 1)-induced epithelial-mesenchymal transition (EMT) in HepG2 cells. Our results showed that stachydrine significantly suppressed TGF-beta 1-induced HepG2 cell migration and invasion in a dose-dependent manner. Stachydrine prevented TGF-beta 1-induced EMT in HepG2 cells, as proved by the increased expression level of E-cadherin and decreased expression levels of N-cadherin and vimentin. In addition, stachydrine attenuated TGF-beta 1-induced upregulation of TGF-beta receptor I (T beta RI) in both protein and mRNA levels. Further mechanism investigations proved that stachydrine prevented TGF-beta 1-induced activation of Smad2/3 and phosphoinositol-3-kinase (PI3K)/Akt/mTOR signaling pathways in HepG2 cells. In conclusion, these findings demonstrated that stachydrine prevented TGF-beta 1-induced EMT in HCC cells through Smad2/3 and PI3K/Akt/mTOR signaling pathways. Thus, stachydrine might be a potential therapeutic agent for the treatment of HCC.Copyright (c) 2021 Wolters Kluwer Health, Inc. All rights reserved.

Automated summary

Stachydrine was found to suppress TGF-β1-induced EMT in HCC cells by inhibiting cell migration and invasion, which was achieved by blocking the activation of Smad2/3 and PI3K/Akt/mTOR signaling pathways.