Synergistic inhibitory effect of wogonin and low-dose paclitaxel on gastric cancer cells and tumor xenografts.

Abstract

To investigate the synergistic inhibitory effects of wogonin (WOG) and chemotherapeutic drugs on growth of gastric cancer cells and tumor xenografts. The IC50 values of WOG, cisplatin (CDDP) and paclitaxel (PTX) in four gastric cancer cell lines were determined by MTS assay. Hoechst staining and the median effect method of Chou-Talalay were used to assess the apoptosis of cells and the interaction of two drugs, respectively. BGC-823-derived xenografts in nude mice were established to investigate the effects of WOG combined with chemotherapeutic drugs in vivo. WOG, CDDP and PTX inhibited the growth of BGC-823, MGC-803, MKN-45 and HGC-27 gastric cancer cells in a dose-dependent manner. WOG combined with CDDP or PTX synergistically inhibited the growth of all gastric cancer cell lines in vitro. In BGC-823, MGC-803, HGC-27 and MKN-45 cell lines, synergisms between WOG and PTX were shown when the fraction affected (Fa) values were <0.45, <0.90, <0.85 and <0.60. While WOG and CDDP had a synergistic inhibitory effect when the Fa values were >0, >0, >0.65 and >0.10. From the results of in vivo experiments using tumor xenografts, WOG and low-dose PTX showed better efficacy than either drug alone. The inhibitory percentages of tumor weight were 61.58%, 20.29%, and 22.28% for the combination, WOG-alone, and low-dose PTX-alone groups, respectively. Notably, WOG combined with CDDP displayed very high toxicity. A synergistic inhibitory effect on growth was observed when WOG was combined with low-dose PTX in gastric cancer cells and tumor xenografts. These findings provide evidence for the design of a clinical trial to test the combination of WOG with low-dose PTX in human gastric cancer.