Abstract:
Objective:To investigate the apoptotic effect exerted on human ovarian cancer cells by both the histone deacetylase inhibitor Trichostatin A(TSA) and the proteasome inhibitor PS-341 and their synergistic effect. Methods:Methyl thiazolyl tetrazolium (MTT) assay was applied to examine the cell viability, Annexin-V/PI apoptosis detection kit was used to determine the apoptosis rate of different groups. Besides, Western blot was introduced to evaluate the expression levels of Bcl-2、Mcl-1 and Bcl-X
L. To furtherly evaluate apoptosis in different groups, the activity of Caspase-3 and expression level of PARP was detected. Results:The cell apoptosis rates which were caused by TSA/PS-341 regimen or TSA, PS-341 alone were different(P<0.05). Western blot showed that after the treatment of TSA and PS-341 combination, Bcl-2、Mcl-1 and Bcl-X
L were down-regulated. Exposure to TSA/PS-341 induced the activity of Caspase-3 and the expression of PARP after 48 h of treatment, and there were significant differences compared with the treatment of drug alone(P<0.001). Conclusion:Low-dose TSA and PS-341 synergistically induce cytotoxicity in ovarian cancer cells, and the effect was much more significant than single drug treatment groups. TSA/PS-341 regimen may represent a potential novel therapeutic strategy for ovarian cancer.