Combination of Matrine and Sorafenib Decreases the Aggressive Phenotypes of Hepatocellular Carcinoma Cells

Background: The aim of this study was to determine the effects of matrine (a natural alkaloid) on sorafenib-induced cytotoxicty against hepatocellular carcinoma (HCC) cells, and to explore the molecular mechanisms involved. Methods: HepG2 and Hep3B cells were treated with matrine alone or in combination with sorafenib, and cell viability and apoptosis were assessed. The involvement of micro (mi)RNA-21 in the action of matrine was examined. Results: Matrine significantly augmented the antiproliferative activity of sorafenib in a dose-dependent manner. Matrine significantly increased apoptosis, coupled with enhanced cleavage of caspase-3 and poly (ADP-ribose) polymerase. miRNA-21-overexpressing HCC cells showed a marked decrease in matrine-induced growth suppression and the expression of phosphatase and tensin homolog (PTEN). The suppressive effect of combining matrine and sorafenib was significantly reduced by miRNA-21 overexpression or PTEN inhibition. Conclusion: Matrine in combination with sorafenib leads to increased cytotoxic effects against HCC cells, at least partially, via the suppression of miRNA-21 and the subsequent induction of PTEN.