Synergistic overcoming of cisplatin resistance in ovarian cancer by combined Astragalus Membranaceus and cisplatin treatment: network pharmacology and experimental validation.

Abstract

Ovarian cancer (OC) is a leading cause of mortality among gynecologic malignancies. Cisplatin (DDP) is a first-line chemotherapy agent, but resistance to DDP often develops, compromising its efficacy. Astragalus membranaceus (AS), a traditional Chinese medicine, has shown promise in enhancing chemotherapy sensitivity due to its anti-inflammatory and immunomodulatory properties. This study investigates the potential of AS to overcome DDP resistance in OC. We integrated multiple independent DDP-resistant OC datasets identified 337 DDP resistance-associated targets. Network pharmacology identified 20 active compounds in AS, with 22 potential targets related to DDP resistance. GO and KEGG analyses revealed enrichment in pathways involving inflammation and cell adhesion. Survival analysis indicated nine genes significantly associated with OC prognosis and immune infiltration. Molecular docking showed strong binding affinities between AS compounds and these targets. In vitro, assays demonstrated that AS combined with DDP significantly inhibited cell proliferation and migration while inducing apoptosis in DDP-resistant OC cells. Western blot analysis confirmed significant changes in critical proteins (IL1B, IL1A, SERPINE1, ITGA2, and AXL) with combined treatment. AS combined with DDP significantly enhances the inhibition of cell proliferation and migration while promoting apoptosis in DDP-resistant OC cells. These findings suggest that AS could be a valuable adjunct to DDP in overcoming chemoresistance in OC, potentially improving patient outcomes.