Sevoflurane induces Ca²⁺ overload and EFHD1 upregulation, driving pyroptosis in SCLC cells

Sevoflurane, a widely utilized inhalational anesthetic, has been shown in previous studies to inhibit the proliferation and invasion of non-small cell lung cancer (NSCLC) cells. However, whether sevoflurane affects the metastasis of small cell lung cancer (SCLC) cells remains unexplored. This study's primary objective was to investigate the mechanism by which sevoflurane induces calcium overload and EFHD1 upregulation, thereby contributing to pyroptosis in SCLC cells. NCI-H446 cells were treated with sevoflurane at concentrations of 0%, 0.6%, 3% and 15%. Cell proliferation was assessed using the CCK8 assay, while cell migration and invasion were analyzed using the Transwell assay. EFHD1 expression was determined by q-PCR and Western blot. Calcium content, ROS levels, and CCO content were measured using respective assay kits, and mitochondrial morphology was observed using transmission electron microscopy. Western blotting was performed to detect the expression of caspase-1 and GSDMD. All procedures were repeated under conditions of EFHD1 overexpression or silencing. Sevoflurane inhibited the proliferation, migration, and invasion of NCI-H446 cells, concurrently exerting a significant pro-pyroptotic effect. This was mediated by mitochondrial calcium overload, EFHD1 upregulation, and subsequent mitochondrial damage-induced pyroptosis. Sevoflurane significantly enhances pyroptosis in NCI-H446 cells, thereby potentially reducing cancer cell dissemination during surgery.