Synergistic inhibitory effect of wogonin and low-dose paclitaxel on gastric cancer cells and tumor xenografts
Abstract
Objective: To investigate the synergistic inhibitory effects of wogonin (WOG) and chemotherapeutic drugs on growth of gastric cancer cells and tumor xenografts.
Methods: 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.
Results: 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.
Conclusions: 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.
Methods: 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.
Results: 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.
Conclusions: 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.