Effect of FoxM1 inhibitor thiostrepton on CDDP chemosensitivity in medulloblastoma Daoy cells

Objective To investigate the effects of FoxM 1 inhibition by thiostrepton on CDDP chemosensitivity in medulloblastoma Daoy cells.Methods Medulloblastoma Daoy cells were cultured in vitro; the inhibitory rates of Daoy cells after the treatments of 1,1.25,1.5,1.75,2,3,5 μmol/L thiostrepton (thiostrepton treatment groups),or 1,2,3,4,5,10,20 and 40 μmol/L CDDP (CDDP treatment groups) or 1 μmol/L thiostrepton combined with 1,2,3,4,5,10,20 and 40 μmol/L cDDP (combination treatment groups) were evaluated by CCK8 assay,and the interaction between thiostrepton and cDDP was analyzed by means of Jin's formulatin.According to the analysis results,Daoy cells were treated with thiostrepton (1 μmol/L) and CDDP (3 μmol/L) combination or either drug alone for 24 h,and then,flow cytometry was used to observe the changes of apoptosis; Western blotting was employed to detect the expressions of FoxM1 and apoptosis-relating proteins of bcl-2,bax,caspase 3 and poly-ADP-ribose polymerase (PARP).Results Thiostrepton and cDDP used alone could inhibit the proliferation of Daoy cells,and there was simple addition or synergistic effect after combined treatment (1,2,3,4 and 5 μmol/L cDDP and thiostrepton).Flow cytometric analysis showed that the apoptosis rate of thiostrepton treatment groups and CDDP treatment groups was significantly higher than that of control groups,while that of combination treatment groups was significantly higher than that of thiostrepton treatment groups and CDDP treatment groups (P＜0.05).Western blotting indicated that the FoxMl expression level in the combination treatment groups and thiostrepton treatment groups was significantly lower than that in the control group (P＜0.05); as compared with that in the thiostrepton treatment groups and CDDP treatment groups,the bcl-2 protein level was significantly lower in the combination treatment groups,while Bax,caspase 3 and PARP protein expressions were significantly increased (P＜0.05).Conclusion Thiostrepton acts synergistically with cDDP in low concentration,and its mechanism may involve in inhibiting FoxM 1 expression,and then,enhancing cDDP-induced apoptosis. Key words: Thiostrepton;  FoxM1;  Cisplatin;  Medulloblastoma;  Chemosensitivity