Dexmedetomidine potentiates cisplatin chemosensitivity in esophageal carcinoma cells via the SREBF1/miR-185-5p/Caspase-1 axis through pyroptosis.

Esophageal carcinoma (EC) remains a major global health challenge, particularly due to limited therapeutic efficacy in advanced stages. This study aimed to elucidate the mechanism by which DEX enhances CDDP chemosensitivity in EC cells through pyroptosis. Our results showed that DEX significantly reduced cell viability and decreased the IC50 of CDDP in resistant EC cells, while increasing the expression of pyroptosis-related markers, including Cleaved Caspase-1, GSDMD-N, IL-1β, and IL-18. In contrast, DSF treatment reduced the chemosensitivity of resistant cells to CDDP. Mechanistically, DEX suppressed the expression of SREBF1 and miR-185-5p. SREBF1 was found to bind to the promoter region of miR-185-5p and promote its transcription, whereas miR-185-5p directly targeted the Caspase-1 3'UTR. Furthermore, overexpression of SREBF1/miR-185-5p, as well as knockdown of Caspase-1, attenuated the chemosensitizing effect of DEX. These findings demonstrate that DEX enhances CDDP efficacy by activating pyroptosis through suppression of the SREBF1/miR-185-5p axis and upregulation of Caspase-1. Collectively, our study identifies a novel regulatory pathway through which DEX enhances CDDP chemosensitivity in EC cells.