Celastrol enhanced the anticancer effect of lapatinib in human hepatocellular carcinoma cells in vitro.

PURPOSE To investigate whether celastrol could show synergism combined with lapatinib in HepG2 human hepatocellular carcinoma (HCC) cell line in vitro. METHODS The effects of treatment with lapatinib and/or celastrol on cell growth were determined using MTT assay. Drug synergy was determined using combination index (CI) methods derived from Chou-Talalay equations using CalcuSyn software. Apoptotic morphology was observed by fluorescence microscope with Hoechst 33258 staining. The expression of EGFR of cell surface was performed by flow cytometry. Changes of apoptotic and growth pathways-related proteins were analysed by Western blotting. RESULTS The combination of celastrol and lapatinib produced strong synergy in growth inhibition and apoptosis in vitro in comparison to single-agent treatments. Moreover, celastrol enhanced the ability of lapatinib to down regulate EGFR protein expression in HepG2 cells. CONCLUSION These data indicate that the combination of celastrol and lapatinib could be used as a novel combination regimen which could hopefully provide strong anticancer synergy in the treatment of HCC.