Objective       To determine the effects of 5-Aza-2′-deoxycytidine (5-

Aza-dC) and trichostatin A (TSA) alone

or in combination on the proliferation

apoptosis

the methylation level of O

6

-methylguanine-DNA methyltransferase (MGMT) and the phosphorylation of NF-κB in human gastric carcinoma cell lines with different differentiation grades (MKN-45 and MGC-803).       Methods       After MKN-45 and MGC-803 cells were treated by 5-Aza-dC

TSA and combination respectively

the cell viability was assayed by CCK-8 kit

and apoptosis by Annexin V-FITC/PI staining. The methylation level of MGMT promoter was determined by methylation specific PCR (MSP)

and mRNA expression by RT-PCR. Western blotting was employed to detect the expression of MGMT

NF-κB p65 and p-NF-κB p65 in the 2 cell lines.       Results       5-Aza-dC or TSA monotherapy and combination significantly inhibited cell growth in a dose- and time- dependent manner in MKN45 and MGC-803 cells

and the combination treatment was more significant in the inhibition (

P

0.05). The monotherapies and combination treatment both improved cell apoptosis

and the combination group [(8.43±1.80)% and (21.75±1.06)%

]

had higher apoptotic rate than the 5-Aza-dC [(7.33±1.18)% and (15.22±1.03)%

]

and TSA [(3.53±1.18)% and (12.66±1.10)%

]

monotherapies（

P

0.05）. The monotherapies and combination treatment all reversed MGMT promoter methylation

and increased its mRNA and protein levels

but the combination treatment showed more significant effects (

P

0.05). The expression levels of NF-κB p65 were significantly reduced in the MKN-45 and MGC-803 cells after monotherapies and combination treatment

and the combination treatment [(12.81±4.18)% and (9.08±2.66)%

]

showed stronger inhibitory effects than the 5-Aza-dC [(39.13±3.38)% and (34.90±4.89)%

]

and TSA [(27.55±5.00)% and (22.11±3.07)%

]

monotherapies（

P

0.05）.       Conclusion       Both 5-Aza-dC and TSA inhibit the proliferation

induce the apoptosis

and enhance MGMT expression by changing the methylation and decreasing NF-κB activity in human gastric carcinoma MKN-45

and MGC-803 cells. And the combination treatment shows more significant effects than either of the 2 drugs.