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BACKGROUND:Gastric cancer(GC)is one of the most common causes of cancer related to death worldwide.The new cases each year of GC have been accounted for nearly one half of global GC population in China.Epigenetic changes is one of the most important mechanisms of gastric cancer.DNA methylation and histone modification are the two predominant forms of epigenetic alteration.CHFR is one of the most important cancer suppressor genes related to gastric cancer.DESIGN: trichostatin A(TSA,histone deaceylase inhibitor)combined with 5-Aza-2-deoxycytidine(5-Aza-dC,methyltransferase inhibitor)to GC cell lines SGC-7901.SETTING: It was divided into control group,5-Aza-dC(10μmol/l)group,TSA(1μmol/l)group and 5-Aza-dC combined with TSA(10μmol/l+1μmol/l)group.PARTICIPANTS: the time-dependent response of 5-Aza-dC or TSA alone and their combination on SGC-7901,they were treated for 24,48 and 72 hours,respectively.The cell proliferation inhibition by MTS method and the inhibition rate.Assay cell apoptosis by flow cytometry,SGC-7901 was treated by 5-Aza-dC or TSA alone and combination for 48 hours.Similarly,the mRNA expression of CHFR gene treated for 48 hours was assayed by RT-PCR,CHFR protein expression was assayed by western blotting,and promoter methylation status of CHFR gene treated was assayed by MSP.MEASUREMENTS: The effect TSA combined with 5-Aza-dC on cell proliferation and CHFR gene expression of SGC-7901.RESULTS: The inhibition rates of SGC-7901 cell treated by 5-Aza-dC alone were 18.9%,27.8%and 34.5%alone,those were 12%,20.6%and 24.1%by TSA alone,and those in two drug combination group were 22%,35%and 42.7%for 24h,48h and 72h,respectively.The apoptosis rate of SGC-7901 cell treated by 5-Aza-dC alone was 11.47%that was 13.57%by TSA alone,and two drug combination group 18.12%for 48h.The relative mRNA expression of CHFR gene was 0.167 ± 0.034 treated by 5-Aza-dC alone,that was 0.132 ± 0.009 by TSA alone group and Combination group was 0.265 ± 0.005 in SGC-7901 cell,while the control mRNA level was as 0.061 ± 0.0001.The relative protein expression of CHFR gene was 0.431 ± 0.020 treated by 5-Aza-dC alone,that was 0.290 ± 0.061 by TSA alone group and Combination group was 0.590 ± 0.048 in SGC-7901 cell while the control protein level was as 0.074 ± 0.006.Methylation status was decrease of CHFR gene treated by 5-Aza-dC and TSA alone group and Promoter unmethylation status of CHFR gene treated by Combination group while methylation of the control was still.CONCLUSION: TSA or 5-Aza-dC can inhibit the proliferation and induce apoptosis of SGC-7901 and decreased the promoter methylation,and improved the expression of mRNA and protein of CHFR gene and have potential candidates of clinical drugs.