Ginsenoside Rg6 Improves Cisplatin Resistance in Epithelial Ovarian Cancer Cells via Suppressing Fucosylation and Inducing Autophagy

Platinum-based chemotherapy remains a mainstay of clinical practice in the standard treatment of epithelial ovarian cancer (EOC). Most patients who receive this treatment, however, develop relapse and drug resistance. Ginsenoside Rg6 (G-Rg6), one of the anticarcinogenic active components in the American ginseng berry, may hold promise in the adjuvant chemotherapy of EOC. In this study, the correlation between fucosylation and cisplatin (cDDP) resistance in EOC cells was validated by gene expression profile analysis and lectin blot. We found that G-Rg6 derived from the American ginseng berry inhibits the cell viability and protein fucosylation of cDDP-resistant EOC cells. G-Rg6-induced G₂/M-cell cycle arrest was proven to result from the autophagy of cDDP-resistant EOC cells. In addition, we observed that G-Rg6 initiates autophagy in cDDP-resistant EOC cells by inhibiting the GRB2-ERK1/2-mTOR axis, and that high concentration of G-Rg6 treatment leads to cell apoptosis. G-Rg6 also enhances cDDP uptake in A2780CP cells by promoting CTR1 expression and suppressing its core fucosylation. Therapies combining cDDP and G-Rg6 display higher efficacy in inhibiting the cDDP-resistant EOC cells in comparison with the sole application of cDDP, exhibiting strong potential for clinical application. G-Rg6 derived from the American ginseng berry can improve cDDP resistance in EOC cells via suppressing fucosylation and inducing autophagy, suggesting its potential in the adjuvant chemotherapy of EOC patients.