[Ginsenoside Rg3 Regulates Cisplatin Resistance in Gastric Cancer by Wnt/β-catenin Signaling Pathway].

Objective To investigate the inhibitory effect of ginsenoside Rg3 combined with cisplatin (DDP) on DDP-resistant cell line SGC-7901/DDP and their molecular mechanism.Methods SGC-7901/DDP cells were divided into four groups including a control group,a ginsenoside Rg3 (40 μg/ml) treatment group,a DDP (1.40 μg/ml) treatment group,and a drug combination treatment group.The proliferation ability of SGC-7901/DDP cells was detected by MTT,EdU,and colony formation assays.The apoptosis ability of SGC-7901/DDP cell was detected by flow cytometry and Hoechst 33342 staining.The protein levels of apoptosis-related markers were detected by Western blotting.The migration ability of SGC-7901/DDP cells was detected by wound healing and Transwell assays.The expression levels of proteins in epithelial-mesenchymal transformation (EMT) and Wnt/β-catenin signaling pathway were determined by Western blotting and immunofluorescence staining.Results Compared with the ginsenoside Rg3 or the DDP treatment groups,the drug combination treatment group inhibited the proliferation ( t =8.062, P =0.001; t =7.090, P =0.002),colony formation ( t =8.062, P =0.001; t =6.144, P =0.004),and migration ( t =7.424, P =0.002; t =4.317, P =0.013),and promoted the apoptosis ( t =5.530, P =0.031; t =6.036, P =0.026) of SGC-7901/DDP cells.Compared with the ginsenoside Rg3 and the DDP treatment groups,the drug combination treatment group down-regulated the expression levels of EMT-associated proteins including vimentin ( t =24.450, P <0.001; t =14.750, P <0.001),Snail ( t =29.640, P <0.001; t =70.700, P <0.001),Slug ( t =89.230, P <0.001; t =87.360, P <0.001),matrix metalloproteinase (MMP) 2 ( t =84.540, P <0.001; t =67.120, P <0.001),and MMP9 ( t =19.010, P <0.001; t =10.890, P <0.001),as well as those of Wnt/β-catenin signaling pathway related proteins including Wnt ( t =35.480, P <0.001; t =14.670, P <0.001),β-catenin ( t =155.800, P <0.001; t =118.100, P <0.001),C-myc ( t =20.870, P <0.001; t =3.334, P =0.029),and cyclin D1 ( t =5.007, P =0.008; t =8.347, P =0.001).Meanwhile,it up-regulated the expression of epithelial cells including E-cadherin ( t =36.450, P <0.001; t =33.810, P <0.001) and ZO-1 ( t =37.060, P <0.001; t =37.030, P <0.001).Conclusion Ginsenoside Rg3 enhanced the sensitivity of SGC-7901/DDP cells to DDP by inhibiting the activity of Wnt/β-catenin signaling pathway.