Abstract: OBJECTIVE To investigate the effect and mechanisms of toosendaninl treatment on enhancing cisplatin-induced apoptosis in lung cancer cells. METHODS MTT assay was performed to measure the cell viability of A549 cells treated with toosendaninl and cisplatin. Western blot analysis was performed to detect the phosphorylation of ATF2, expression of Bcl-xl, release of cytochrome C and activation of caspase-9 and caspase-3 in A549 cells treated with toosendaninl and cisplatin. Flow cytometry analysis was performed to measure the cell apoptosis of A549 cells treated with toosendaninl and cisplatin. RESULTS Results of MTT assays showed that toosendaninl treatment decreased the IC₅₀ of cisplatin to A549. Results of Western blot analysis showed that toosendaninl treatment inhibited the expression and phosphorylation of ATF2 in A549 cells treated with cisplatin. In addition, transfection with ATF2 plasmid abolished the synergistic effect of toosendaninl on cisplatin-induced cell death. Results of Western blot and flow cytometry analysis toosendaninl treatment inhibited the cisplatin-induced upregulation of Bcl-xl, and thus promoting release of cytochrome C, activation of caspase-9 and caspase-3 and cell apoptosis. CONCLUSION toosendaninl enhances cisplatin-induced apoptosis in lung cancer through promoting the phosphorylation of ATF2.