Euphorbia factor L2 inhibits TGF-β-induced cell growth and migration of hepatocellular carcinoma through AKT/STAT3

Background: Euphorbia factor L2 has potent effects on ascites, hydropsy and cancers. Purpose: We investigated the pharmacological effects of Euphorbia factor L2 (EFL2) on hepatocellular carcinoma (HCC). Methods: MTT assay was conducted to determine the proliferative activity of EFL2 on Hep G2 and SMMC-7721 cells. Wound-healing assay, colony formation assay, western blotting and quantitative PCR were carried out to examine the cell migration, p-AKT and p-STAT3 signaling. Moreover, we used human tumor xenograft BALB/c nude mice to detect the effect of EFL2 on HCC in vivo. Results: EFL2 inhibited the proliferation of SMMC-7721 and Hep G2 cells in concentration- and time-dependent manners. EFL2 also suppressed the cell migration and colony formation of hepatocellular carcinoma cells. Using a transforming growth factor-beta (TGF-beta)-induced epithelial-mesenchymal transition (EMT) model, we provided evidences that EFL2 could also inhibit TGF-beta induced cell growth, vimentin, N-cadherin expressions, activation of p-AKT and p-STAT3, whereas up-regulate E-cadherin expression. Furthermore, EFL2 inhibited tumor growth and STAT3 phosphorylation in vivo. Conclusion: In conclusion, EFL2 has the potential to be explored as a candidate treatment agent for HCC by inhibiting cell growth and migration both in vitro and in vivo.