[Evodiamine enhances the killing effect of NK cells on small cell lung cancer by regulating BIRC5]

Objective To investigate the effects of evodiamine (EVO) on Natural Killer (NK) cell-mediated killing in small cell lung cancer (SCLC) cells via affecting baculoviral inhibitor of apoptosis repeat containing 5 (BIRC5). Methods H446 cells and NK-92 cells were treated with EVO at different concentrations, and cell proliferation was detected using the MTT (3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay, while cell invasion was assessed using the Transwell^TM assay. NK-92 cells and H446 cells were co-cultured at different effector-to-target ratios to detect the cytotoxicity of NK cells against H446 cells and the level of degranulation in NK-92 cells. Network pharmacology was employed to analyze the potential targets of EVO in the treatment of SCLC, and further validation was conducted to elucidate the mechanism of EVO's action in SCLC. An xenograft tumor model was used to evaluate the effect of EVO on tumor growth. Results Compared with the control group, EVO treatment dose-dependently inhibited the proliferation and invasion of H446 cells, while enhancing the cytotoxicity of NK-92 cells against H446 cells and the level of NK-92 cell degranulation. Network pharmacological analysis revealed that BIRC5 is a core target of EVO in the treatment of SCLC, and EVO suppressed the expression of BIRC5 protein without affecting BIRC5 mRNA expression. In vivo studies demonstrated that EVO inhibited tumor growth in a dose-dependent manner. Conclusion EVO promotes the degradation of BIRC5, thus enhancing the killing effects of NK cells on SCLC cells.