DNA (cytosine-5-)-methyltransferase 1 (DNMT1) plays an important role in the 
maintenance of DNA methylation patterns via complicated networks including 
signaling pathways and transcriptional factors, relating to cell differentiation 
or carcinogenesis. In the present study, we designed an antisense 
oligodeoxynucleotide of DNMT1 (AS/MT: 5'-CGGTAC GCGCCGGCATCT-3') and 
demonstrated successful inhibition of DNMT1 expression by AS/MT at the protein 
level, using gastric cancer cell lines in vitro. E-cadherin protein expression 
was increased, and both cyclin D1 and PCNA were decreased by AS/MT treatment. 
AS/MT also induced suppression of cell growth as determined by BrDU uptake 
incorporation, in a dose-dependent manner, suggesting specificity of AS/MT. 
Simultaneously, morphological alterations were observed in both TMK-1 and MKN-45 
cells after 24 h incubation with 2 micro M of AS/MT. The cells changed shape 
from their original forms to dispersed, fibroblast-like cells with neurite-like 
processes, accompanied by an increased adhesive potential of the cells. An in 
vivo model of peritoneal dissemination using the nude mouse system showed an 
increased malignant potential of AS/MT treated TMK-1 cells as demonstrated by a 
greater number of peritoneal tumor nodules in the AS/MT as compared to the NS/MT 
treated group, 34.8+/-4.3 vs. 22.4+/-3.0 nodules, respectively (p=0.0039). The 
total wet tumor weight in the AS/MT group (350+/-47.4 g) was significantly 
greater than that in the NS/MT group (248+/-41.5 g) (p=0.0065). In conclusion, 
the inhibition of DNA methylation by DNMT1 by an antisense oligodeoxynucleotide 
influences cell morphology and adhesion, as well as cell growth in gastric 
cancer cells in vitro. Moreover, these alterations in the characteristics of 
cancer cells resulted in an increased ability to attach onto the peritoneum in 
the nude mouse system in vivo, suggesting that strict clinical guidelines will 
be necessary to utilize such a DNA methylation inhibitor, since it does not 
always mean a therapeutic antitumor strategy.