Objective:The chemo-preventative and therapeutic properties of selenium nanoparticles (SeNPs) have been documented over recent decades and suggest the potential uses of SeNPs in medicine.Biogenic SeNPs have higher biocompatibility and stability than chemically synthesized nanoparticles,which enhances their medical applications,especially in the field of cancer therapy.This study evaluated the potential of green-synthetized SeNPs by using berberine (Ber) as an antitumor agent and elucidated the mechanism by which these molecules combat Ehrlich solid tumors (ESTs).Methods:SeNPs containing Ber (SeNPs-Ber) were synthesized using Ber and Na2SeO3 and characterized with Fourier transform infrared spectroscopy.Sixty male Swiss albino mice were then acclimatized for one week,injected with Ehrlich ascites tumor cells,and divided into four groups:EST,EST + cisplatin(5 mg/kg),EST + Ber (20 mg/kg),and EST + SeNPs-Ber (0.5 mg/kg).At the end of a 16-day observation period,12 mice from each group were euthanized to analyze differences in the body weight,tumor size,gene expression,and oxidative stress markers in the four groups.Three mice from each group were kept alive to compare the survival rates.Results:Treatment with SeNPs-Ber significantly improved the survival rate and decreased the body weight and tumor size,compared to the EST group.SeNPs-Ber reduced oxidative stress in tumor tissue,as indicated by a decrease in the lipid peroxidation and nitric oxide levels and an increase in the glu-tathione levels.Moreover,SeNPs-Ber activated an apoptotic cascade in the tumor cells by downregulating the B-cell lymphoma 2 (Bcl-2) expression rate and upregulating the Bcl-2-associated X protein and caspase-3 expression rates.SeNPs-Ber also considerably improved the histopathological alterations in the developed tumor tissue,compared to the EST group.Conclusion:Our study provides a new insight into the potential role of green-synthesized SeNPs by using Bet as a promising anticancer agent,these molecules could be used alone or as supplementary medica-tion during chemotherapy.