Exploring the Molecular Mechanism of Phenethyl Alcohol Glycoside's Anti-Cervical Cancer Activity Based on Network Pharmacology

Abstract

Cervical cancer is one of the most common and most threatening malignant tumors of the female reproductive system worldwide, with an incidence markedly higher than that of endometrial and ovarian cancers. There is an urgent need for multi-target, low-toxicity therapeutic strategies. This study, based on network pharmacology integrated with experimental validation, systematically investigates the molecular mechanisms by which phenylethanoid glycosides (PhGs: echinacoside, acteoside, isoacteoside, and 2-acetylacteoside) act against cervical cancer. Overlapping targets between PhGs and cervical cancer were screened using databases such as SwissTargetPrediction and GeneCards; a protein–protein interaction (PPI) network was constructed with STRING to identify hub genes. Target expression was verified using the GEPIA and HPA databases, and GO/KEGG enrichment analyses were performed via Metascape. Finally, CCK-8, colony-formation, Transwell, and ELISA assays were employed to verify the effects of PhGs on the proliferation, migration, and inflammatory cytokine secretion of HeLa and SiHa cervical cancer cells. In total, 27 common targets were identified, of which 15 were hub genes (e.g., CASP3, MMP9, AKT1). KEGG enrichment indicated that PhGs mainly regulate the PI3K–Akt, MAPK, mTOR, VEGF, and IL-17 signaling pathways. Experimental results confirmed that PhGs inhibit cervical cancer cell proliferation, colony formation, and migration in a concentration-dependent manner. In summary, by coordinately controlling key targets related to apoptosis (CASP3), metastasis (MMP9), inflammation (TNF/IL-6), and the PI3K–Akt/MAPK pathways, PhGs suppress the progression of cervical cancer, and their multi-target mechanism provides a theoretical basis for the development of adjuvant therapeutics for this disease.