IgG Fc binding protein (FCGBP) inhibits the development of laryngeal squamous cell carcinoma and cisplatin resistance through the PIGR/JAK2/STAT3 pathway.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is the second most common malignancy of the head and neck, and one of the major therapeutic challenges is resistance to cisplatin (CDDP). IgG Fc binding protein (FCGBP), known as a tumor suppressor in various cancers, has also been implicated in drug resistance. This study investigated the role of FCGBP in LSCC. MATERIALS AND METHODS: The expression and prognostic relevance of FCGBP were initially analyzed using the Gene Expression Profiling Interactive Analysis 2 (GEPIA2) database. The in vivo effects of FCGBP were examined using a nude mouse xenograft model of LSCC, and its in vitro effects were assessed through half-maximal inhibitory concentration (IC(50)) analysis, colony formation assays, and flow cytometry. The underlying mechanism by which FCGBP modulates CDDP resistance was invstigated by silencing the polymeric immunoglobulin receptor (PIGR). RESULTS: FCGBP was significantly downregulated in head and neck squamous cell carcinoma (HNSCC) tissues and LSCC cell lines, and its reduced expression was associated with poor prognosis. It inhibited the viability and proliferation of LSCC cells by approximately 50% and reduced their resistance to CDDP, lowering the IC(50) from 50 μM to approximately 30 μM. Mechanistically, FCGBP modulated the PIGR/JAK2/STAT3 signaling pathway, thereby exerting both anti-tumor and anti-CDDP resistance effects. In vivo, FCGBP overexpression significantly suppressed LSCC tumor growth, with tumor volume reduced by approximately 67%. CONCLUSIONS: These findings suggest that the FCGBP/PIGR/JAK2/STAT3 axis regulates CDDP resistance in LSCC and that FCGBP may serve as a potential therapeutic target to improve cisplatin efficacy in treating LSCC.