Experimental study on the antitumor effects of oxymatrine combined with cisplatin by down-regulating Bcl-2 expression and up-regulating Bax expression in ovarian cancer

doi:10.3969/j.issn.1002-7386.2015.22.004

Abstract：Objective To investigate the antitumor effects of oxymatrine combined with cisplatin by down-regulating Bcl-2 expression and up-regulating Bax expression in ovarian cancer, and to explore the action effects of Bcl-2 and Bax on ovarian cancer in vitro and in vivo.Methods Fifty female Fisher344 rats were injected with NuTu 19 cells hypodermically to establish solid tumor models with ovarian cancer, then the tumor-bearing rats were randomly divided into 5 groups: model group, cisplatin group (3mg/kg), cisplatin+oxymatrine tumor weights (40mg/kg,80mg/kg,160mg/kg) groups,with 10 rats in each group.After 12-day treatment, the tumor weight was measured and the inhibition rate on tumor was calculated. Apoptosis rate of tumor cells was detected by flow cytometry.The ovarian cancer cell strain-SKOV3 O was divided into three groups:blank control group, cisplatin group, cisplatin +oxymatrine ( 2.5mg/ml, 5.0mg/ml, 10.0mg/ml ) groups, after 48-hour treatment, the cell proliferation was detected by MTT, cell cycle and cell apoptosis rate were measured by flow cytometry (FCM) and the expresson levels of Bcl-2,Bax protein were detected by Western Blot.Results Moreover,inhibition tumor rate was significantly increased ( P <0.05) .As compared with that in cisplatin group, the apoptosis rate of tumor cells was significantly increased in oxymatrine groups,especially in 160mg/kg group ( P <0.05).As compared with that in cisplatin group, the proliferation of SKOV3 cells was significantly inhibited by oxymatrine, especially in 5.0mg/ml group and 10.0mg/ml group ( P <0.05),with a dose-dependent way.As compared with that in cisplatin group, the percentage of cells in G0/G1 phase was significantly increased in oxymatrine groups ( P <0.05),moreover,cell apoptosis rate in cisplatin+oxymatrine groups was increased at some extent,as compared with that in cisplatin group, there was a significant difference between oxymatrine 10.0mg/ml group and cisplatin group ( P <0.05).The expression levels of Bcl-2 protein were decreased by oxymatrine,there were significant differences between oxymatrine 5.0mg/ml group, 10.0mg/ml group and cisplatin group (P<0.05).However the expression levels of Bax protein were increased by oxymatrine,there were significant differences between oxymatrine 10.0mg/ml group and cisplatin group ( P <0.05).Conclusion Oxymatrine can enhance the inhibitory effect of cisplatin on growth of ovarian cancer, which may be completed partly by down-regulating expression of Bcl-2 and up-regulating expression of Bax,moreover, by inducing cell apoptosis of ovarian cancer.