Background and Objective: S-adenosylmethionine(SAM),the most important methyl donor in human body,is generally used to treat cholestesis in clinic.In recent years,SAM has been found to have inhibitory effects on breast cancer,liver cancer and colon carcinoma.This study was to investigate the inhibitory effects of SAM on human gastric cancer cells in vivo and in vitro,and the antitumor mechanisms.Methods: The effects of SAM on the proliferation of gastric cancer SGC-7901 and MKN-45 cells were determined by MTT assay.After SGC-7901 and MKN-45 cells were treated with 0,2,and 4 mmol/L SAM for 72 h,the expression and methylation of c-myc and uroldnase type plasminogen activator(uPA)were detected by reverse trenscription-polymerase chain reaction(RT-PCR)and methylation-specific PCR(MSP).Tumor xenografts were established by injecting SGC-7901 cells subcutaneously in BALB/c nude mice.The mice control group[normal saline(NS)],and received peritoneal injection of relative reagents for 15 days.The tumor size was measured,the protein and mRNA expression of c-myc and uPA were detected by immunohistochemistry and RT-PCR,and the methylation of c-myc and uPA genes was detected by MSP.Results: SAM inhibited the growth of SGC-7901 and MKN-45 cells obviously and the effects were enhanced with the increase of SAM concentration and treatment time.The mRNA expression of c-myc and uPA in SGC-7901 cells and that of uPA in MKN-45 cells significantly decreased.The cmyc and uPA genes in SGC-7901 cells and uPA gene in MKN-45 cells were partly or completely methylated after SAM treatment.The tumor volume was significantly lower in low concentration group[(618.51±149.27)mm3]and high concentration group[(444.32±118.51)mm3]than in control group[(1018.22±223.07)mm3](both P