Study Of The Expression Profiling In MOLT-4 Treated With Trichostatin A(TSA) TSA Increases The Efficiency Of Cisplatin On Human Ovarian Cancer Cell C13* In Vitro

Object: Using a cDNA microarray to investigate the expression profiling of MOLT-4 cells treated with Trichostatin A(TSA), analyse and identify the differentially regulated genes related to apoptosis subsequently.Methods: To confirm the time course of apoptosis in MOLT-4 cells induced by different concentrations of TSA. To induce apoptosis in MOLT-4 by treated with 200nmol/L TSA. To prepare the samples for a cDNA microarray by collecting cells at multiple time-point after TSA treatment. The data of microarray were analysed by bioinformation techniques to investigate the expression profiling. The regulated gene STAT5a was chosen to verify by RT-PCR and western blot.Results: Apoptosis of MOLT-4 induced by 200nmol/L TSA starts at 8 hours later after drug treatment and climaxes at about 36 hours. The data of microarray shows that the gene expression is activated and the number of differentially regulated genes grows up along the time course. Apoptotic genes such as DAPK3,STK4,TNFRSF25,IER3 are found and STAT5a is chosen to verify by RT-PCR and western blot. MOLT-4 cells transfected with STAT5a antisense ODNs are sensitive to TSA than those transfected with STAT5a scrambled ODNs.Conclusions: TSA activates genes expression of MOLT-4 and STAT5a maybe a key mediator of TSA induced-apoptosis. Objective: This study was designed to investigate the synergic effect of Histone deacetylase inhibitors, trichostatin A (TSA), and cisplatin (DDP), on cisplatin-resistant ovarian epithelial cancer cell line C13* and to explore its possible application in reversing the chemotherapy-resistance of cancer cells.Methods: The effect of TSA and/or CDDP on the cytotoxicity to C13* was detected by MTT assay and clonogenic survival assays. Apoptotic cells were evaluated by both morphological assessment of Hochest 33258 and flow cytometry. The cell cycle was also analyzed by flow cytometry.Results: The apoptotic rates induced by treatment with 40nmol/L TSA was2.99%, there was minimally effect on proliferation at this dose. Preincubation with a subtoxic concentration of TSA markedly sensitized C13* cell to cisplatin.Conclusions: Pretreatment with TSA can increase the efficiency of cisplatin on human ovarian cancer cells in vitro which is promising for future clinical application.