Ginsenoside Rb1 inhibits hypoxia-induced epithelial-mesenchymal transition in ovarian cancer cells by regulating microRNA-25.

Metastasis frequently occurs in advanced ovarian cancer, which not only leads to substantial mortality but also becomes a major challenge to effective treatment. Epithelial-mesenchymal transition (EMT) is a key mechanism facilitating cancer metastasis. Targeting the EMT process with more efficacious and less toxic agents to prevent metastasis is of significant therapeutic value for ovarian cancer treatment. The anti-EMT function and mechanism of ginsenoside Rb1, a monomer composition extracted from the traditional Chinese herb or , was investigated in the present study. Western blotting demonstrated that treatment with ginsenoside Rb1 antagonized hypoxia-induced E-cadherin downregulation and vimentin upregulation in SKOV3 and 3AO human ovarian cancer cells. Wound healing assays and migration assays indicated that ginsenoside Rb1 weakened hypoxia-enhanced cell migration ability. Furthermore, it was demonstrated that microRNA (miR)-25 is upregulated by hypoxia in ovarian cancer cells, which was attenuated by ginsenoside Rb1 treatment. Additionally, forced expression of miR-25 in ovarian cancer cells was identified to not only trigger EMT, but also block the suppressive effects of ginsenoside Rb1 on hypoxia-induced EMT by negatively targeting the E-cadherin transactivator, EP300. In conclusion, ginsenoside Rb1 may reverse hypoxia-induced EMT by abrogating the suppression of miR-25 on EP300 and E-cadherin, which suggests that ginsenoside Rb1 may be a potential therapeutic candidate for the treatment of ovarian cancer.