Synergy effect of deoxyschizandrin and gemcitabine on proliferation of HepG2 human hepatocellular carcinoma cells / 中国药理学通报

ABSTRACT

Aim To investigate the synergy effects of deoxyschizandrin and gemcitabine (GEM) on the proliferation of HepG2 human hepatocellular carcinoma cells in vitro and the underlying mechanism. Methods CCK8 method and colony formation assay were used to detect the effects of deoxyschizandrin monotherapy, GEM monotherapy and combination therapy on the proliferation of HepG2 cells. Flow cytometry was used to detect the change of apoptosis rate of HepG2 cells after treatment with single drug or the combination use of two drugs. Western blot was performed to detect the expression of BCL2, BAX, pro-caspase3, caspase3, pro-caspase9, caspase9, ß-catenin and TCF-4. Results Deoxyschizandrin, GEM and combination group significantly inhibited the proliferation of HepG2 cells and promoted cell apoptosis. The effects of the combination group on HepG2 cells were significantly stronger than those of single-drug groups (P < 0. 05). Western blot results showed the expression of pro-caspase3 and pro-caspase9 was changed slightly within deoxyschizandrin, GEM and combination groups compared with that of normal control, while the expression of B C L 2, ß-catenin and TCF-4 protein expression was down-regulated significantly (P < 0. 05). The expression of B A X, cleaved-caspase3 and cleaved-caspase 9 protein increased significantly after treatment with deoxyschizandrin, GEM and combination group (P < 0. 05). Specially, the increasing effect of the expression of the protein in combined group was more significant than that of single drug groups (P < 0. 05). Conclusions The combination of deoxyschizandrin and GEM significantly inhibited the proliferation of HepG2 cells and induced cell apoptosis, as well as suppressed the ß-catenin/TCF-4 pathway.