Synergistic effects of sorafenib and cilostazol in HepG2 cells

Sorafenib, an established multi-kinase inhibitor, is a cornerstone treatment for advanced hepatocellular carcinoma (HCC). This study evaluated the efficacy of combining sorafenib with cilostazol, a phosphodiesterase-3 inhibitor with emerging anticancer properties, in HepG2 cells. Cell proliferation, apoptosis, and expression of VEGF, SMAD4, Bcl-2, TGF-beta, Bax, and caspase-3 were assessed. Combination treatment significantly reduced the IC50 of sorafenib and markedly decreased colony formation compared with either monotherapy. Enhanced apoptosis was observed through increased Bax and caspase-3 levels and reduced Bcl-2 expression. In addition, combined treatment produced potent anti-angiogenic effects through suppression of VEGF and TGF-beta. These findings demonstrate a synergistic interaction between sorafenib and cilostazol and suggest that this combination may represent a promising therapeutic strategy for hepatocellular carcinoma management.