Objective To investigate the impact of spermidine on proliferation and apoptosis of diffuse large B-cell lymphoma(DLBCL)cell lines.Methods The impact of spermidine on cellular growth was assessed using a CCK-8 assay.Flow cytometry was employed to investigate the effects of spermidine on the proliferation and cell cycle dynamics of DLBCL cell lines,as well as to evaluate its influence on apoptosis in DLBCL cell lines,mouse splenocytes,and peripheral blood mononuclear cells(PBMCs)derived from healthy individuals.Western blot analysis was conducted to examine alterations in protein expression levels associated with apoptosis and the cell cycle following treatment with spermidine.Results The CCK-8 assay revealed a significant inhibitory effect of spermidine on DLBCL cell growth(P<0.001).Flow cytometric analysis demonstrated that spermidine had no impact on the proliferation or cell cycle of DLBCL cells,but significantly induced apoptosis(P<0.001).Spermidine exhibited a pro-apoptotic effect on mouse splenocytes(P<0.01),albeit weaker compared to its effect on DLBCL cells(P<0.001),and showed no significant pro-apoptotic effect on PBMCs.Western blot results indicated that spermidine did not influence the expression levels of cell cycle proteins CDK2 and CDK4,but enhanced the activation of Caspase-9 in A20 cells and Caspase-8 in OCI-Ly3 cells.Conclusion Spermidine induces apoptosis and suppresses cell growth in DLBCL cell lines,while exhibiting diminished or absent pro-apoptotic effects on mouse splenocytes and healthy human PBMCs,suggesting its potential as a specific inhibitor for the growth of DLBCL cell lines in vivo.