Tanshinone IIA inhibits epithelial-mesenchymal transition in ovarian cancer by promoting NR3C2 transcriptional activation of ING1.

Ovarian cancer (OV) is among the most lethal forms of gynecological cancers. This work aims to investigate the roles and underlying mechanisms of Tanshinone IIA (Tan IIA) in the epithelial-to-mesenchymal transition (EMT) process in OV. Tan IIA inhibited OV cell proliferation, migration, invasion, and EMT in a dose-dependent manner. Knockdown of nuclear receptor subfamily 3 group C member 2 (NR3C2) weakened the efficacy of Tan IIA, while combined overexpression of inhibitor of growth protein 1 (ING1) rescued the OV progression promoted by NR3C2 knockdown. NR3C2 occupied the ING1 promoter to exert transcriptional activation. Patients with low NR3C2/ING1 expression were associated with more advanced FIGO staging, larger ascites volume, and peritoneal metastasis, and had significantly poorer survival outcomes. Collectively, Tan IIA upregulates NR3C2 expression and activates ING1 transcription to exert its anti-metastatic effects by inhibiting EMT in OV. The study also underscored the prognostic potential of NR3C2/ING1 for OV.