Proteasome inhibitors sensitize ovarian cancer cells to paclitaxel induced apoptosis / 中华妇产科杂志

ABSTRACT

Objective To explore the semitivity of ovarian cancer cell line SKOV3 to paclitaxel,oroteasome inhibitors,bortezomib,and their combination.Methods The methyl thiazolyl tetrazolitim (MTT)assay was applied to examine the cell viability after treatment.The annexin V-propidium iodide apoptosis detection kit was used to determine the apoptosis rate of different groups.Western blot assay was used to evaluate the expression levels of phosphorylated protein kinase B(AKT)and glycogen synthase kinase-3 beta(GSK-3β).Results In MTT assay,the cell viability ratios of the combination group at serial time points from 12,24,36,48 and 72 hours Were(65.2±5.8)%,(58.3±14.4)%,(35.3±5.0)%,(19.2±1.5)%,and(11.4 ±2.5)%,which were significantly lower than those of the paclitaxel group (P<0.05).After arug treatments,apoptosis rates of paclitaxel group,bortezomib group and the combination group were (14.7±0.5)%,(15.1±0.8)%and(20.5±0.7)%respectively.The rate of the combination group was significantly higher than that of non-treated group and paclitaxel group(P<0.05).Western blot assay showed the changes in expression levels of phosphorylated AKT and GSK-3β,which were decreased significantly after paclitaxd and bortezomib combination treatment [(3.2±0.8)%,(19.3±0.4)%;P<0.05].Conclusions The lethal effect of paclitaxel on tumor cells could be increased significantly by its combination with proteasome inhibitors,bertezomib.The AKT/GSK-3β signaling pathway plays an important role in the molecular mechanism of the combination treatment.