Metformin reverses stem cell‑like HepG2 sphere formation and resistance to sorafenib by attenuating epithelial‑mesenchymal transformation.

Cancer stem cells (CSCs) have been reported to be associated with the recurrence and drug resistance of liver cancer. In the present study, stem cell-like HepG2 cell spheres were enriched using stem cell conditioned culture medium. As expected, stem-like HepG2 cell spheres exhibited increased resistance to sorafenib. Metformin, a common drug used to treat type 2 diabetes mellitus, reduced the diameters and numbers of stem-like HepG2 spheres, and increased their sensitivity to sorafenib. Western blotting confirmed that low doses of metformin reversed the epithelial-mesenchymal transformation (EMT) process of HepG2 spheres. These results suggested that metformin enhanced sensitivity to sorafenib, which was probably through reversal of the EMT process of sphere-forming cells and by reducing the formation of CSCs.