Effect of fibrinogen like protein 1 on cisplatin-resistance in laryngeal carcinoma through targeting integrinβ1 in vivo and in vitro.

OBJECTIVE: To explore the relationship between fibrinogen like protein 1 (FGL1) and cisplatin (CDDP) resistance in laryngeal carcinoma, as well as dissect the underlying molecular regulatory pathways. METHODS: The functional roles of FGL1 in cell proliferation, migration, invasion, and apoptosis were confirmed using the CCK-8 proliferation assay, wound healing assay, transwell invasion assay, and flow cytometry-based apoptosis quantification. In order to further elucidate the impact of FGL1 downregulation on tumor growth, a subcutaneous xenograft tumor model was established. TUNEL staining for apoptotic cells, immunohistochemical (IHC) analysis and western blot analysis were performed to detect the number of apoptotic cells and expression profiles of key regulatory proteins. RESULTS: FGL1 knockdown significantly suppressed the proliferative capacity, migratory potential, and invasive ability of CDDP-resistant laryngeal carcinoma cells while inducing marked apoptosis. Mechanistic investigations revealed that inhibition of FGL1 could suppress cellular resistance to CDDP and downregulate drug-resistant proteins by blocking its direct interaction with Integrinβ1, specifically leading to downregulation of CDDP-resistant effector proteins, namely multidrug resistance-associated protein 1 (MRP1) and B-cell lymphoma-2 (Bcl-2). In the xenograft model, FGL1 depletion attenuated tumorigenic potential of TU212-R cells, enhanced CDDP chemosensitivity, and counteracted Integrinβ1-mediated oncogenic signaling hyperactivation. CONCLUSION: FGL1 plays a pivotal role in CDDP resistance development by activating the Integrinβ1-dependent pro-survival pathway in laryngeal carcinoma. Therapeutic targeting of FGL1 may represent a promising strategy to circumvent chemoresistance and improve clinical outcomes for CDDP-resistant laryngeal cancer patients.