Peng Chu

Integrated network pharmacology and experimental models uncover the mechanism of procyanidin B2 against ovarian carcinoma via EGFR/AKT pathway

Ovarian carcinoma (OC) remains a lethal malignancy with limited therapeutic options. Procyanidin B2, a natural flavonoid, has demonstrated broad bioactivity, yet its potential role in ovarian cancer remains incompletely understood. This study employed an integrated approach combining network pharmacology, molecular docking, and experimental validation to elucidate the anti-tumor mechanisms of Procyanidin B2 in ovarian cancer. Through multi-database screening, 97 potential targets of Procyanidin B2 related to OC were identified. Functional enrichment analyses highlighted significant involvement in cancer-related pathways such as PI3K-Akt, HIF-1 and EGFR tyrosine kinase inhibitor resistance. Protein-protein interaction network analysis identified 10 hub genes, among which EGFR and AKT1 were prioritized. Molecular docking confirmed strong binding interactions between Procyanidin B2 and these targets, particularly EGFR. In vitro assays revealed that Procyanidin B2 selectively inhibited proliferation and colony formation, and induced apoptosis in A2780 and SKOV3 cells, accompanied by upregulation of cleaved caspase-3 and suppression of phosphorylated EGFR and AKT. In a xenograft model, Procyanidin B2 administration significantly suppressed tumor growth without evident toxicity, consistent with the in vitro signaling alterations. These results suggest that Procyanidin B2 exerts anti-ovarian cancer effects partly through modulating the EGFR/AKT signaling axis, supporting its potential as a complementary therapeutic candidate.

Isoginkgetin as a novel USP8 inhibitor discovered by structure-based virtual screening exerts anticancer effects in ovarian cancer

Ubiquitin-specific protease 8 (USP8) gene has been identified as being significantly amplified and overexpressed in Ovarian carcinoma (OC), and thus led to unfavorable clinical outcomes, implying that inhibition of USP8 may be a therapeutic strategy for OC. Herein, a structure-based discovery and bioassays were conducted to identify novel inhibitors of USP8. we employed a novel platform that integrates docking/molecular dynamics (MD) simulation/binding free energy calculations/root-mean-square deviation (RMSD)/USP8 enzyme activity assay to screen a library of bioactive compounds including 30000 compounds. we identified that Isoginkgetin exhibited promising inhibitory activity on USP8 with an IC50 value of 12.68 μM. Moreover, Isoginkgetin could significantly inhibit OC cell growth by suppressing cell proliferation and reducing colony formation, and promoting Fe