Licoricidin suppresses growth and metastasis of hepatocellular carcinoma by targeting PI3K/AKT signaling

Abstract

Background

Licoricidin is a prenylated isoflavone isolated from Glycyrrhiza uralensis Fisch, and its biological activities and pharmacological properties have been reported in recent years. This study comprehensively explored the licoricidin’s effect on hepatocellular carcinoma (HCC) and elucidated its underlying mechanism.

Methods

HCC Hep3B and Huh-7 cells were treated with licoricidin at various concentrations. The experimental methods in vitro, including CCK-8, colony formation, EdU, flow cytometry, wound healing, and transwell were performed to evaluate the licoricidin’s effect on HCC cell proliferation, apoptosis, migration, and invasion. The antitumor and anti-metastasis activities of licoricidin were validated using a Hep3B xenograft model and a metastasis model. Western blot or RT-qPCR was used to measure the levels of apoptosis–, epithelial-mesenchymal transition–, and PI3K/AKT–related proteins.

Results

The results indicated that the antiproliferation effect of licoricidin in HCC was related to cell cycle arrest (S phase) and apoptosis induction. Licoricidin upregulated Bax and cleaved caspase3/9 expression and downregulated Bcl-2 expression in cancer cells. In a subcutaneous xenograft model, licoricidin treatment suppressed the growth of tumor. Nontoxic concentrations of licoricidin reduced the migration and invasion abilities of HCC cells. Licoricidin downregulated N-cadherin and vimentin expression, while upregulating E-cadherin expression. Licoricidin treatment reduced the number of metastatic lung nodules in a metastasis model. Inhibition of PI3K/AKT signaling might be a potential mechanism behind the licoricidin’s anticancer effect.

Conclusion

Overall, licoricidin suppresses growth and metastasis of HCC by targeting.

PI3K/AKT signaling, suggesting that licoricidin might be a promising candidate for HCC treatment.