[Effects of S-adenosylmethionine on gastric cancer cell lines SGC-7901 and BGC-823].
OBJECTIVE
To observe the effects of S-adenosylmethionine (SAM) on cell proliferation, cell cycles, apoptosis and invasive capacity of gastric cancer cell lines SGC-7901 and BGC-823 and detect the methylation status and expression of c-myc and urokinase-type plasminogen activator (uPA).


METHODS
The effect of SAM on proliferation of SGC-7901 and BGC-823 cells were determined by MTT assay. SGC-7901 and BGC-823 cells were treated with different concentrations of SAM (0, 2, 4 mmol/L) for 72 h. Then flow cytometry was used to detect the change of cell cycles and apoptosis; Transwell assay to detect the invasion; RT-PCR and Western blot to detect the expression of c-myc and uPA; and MSP to detect the methylation of c-myc and uPA.


RESULTS
SAM displayed a growth-inhibiting effect on SGC-7901 and BGC-823 cells in a dose- and time-dependent manner after exposure to SAM at different concentrations (0.5 - 32 mmol/L) for 24, 48 and 72 h, cell proliferation were significantly restrained (all P < 0.05); 72 h IC50 SGC-7901 5.40 mmol/L and BGC-823 4.01 mmol/L. After treating SGC-7901 and BGC-823 with different concentrations of SAM, the cell percentages of G0/G1 phase significantly increased (P < 0.05 and P < 0.01) while the cell proliferation indices significantly decreased (P < 0.05 and P < 0.01). Compared with control group (0.33 +/- 0.09), the cell apoptosis of 2 mmol/L (5.79 +/- 0.75) and 4 mmol/L groups (10.19 +/- 0.60) of SGC-7901 were obviously reduced (all P < 0.01). Compared with control group (0.95 +/- 0.19), the cell apoptosis of 2 mmol/L (6.23 +/- 0.75) and 4 mmol/L groups (11.82 +/- 1.14) of BGC-823 were obviously reduced (all P < 0.01). The cell invasive capacity were significantly restrained (P < 0.01). The invasion inhibition ratio of 2 mmol/L and 4 mmol/L groups of SGC-7901 were 51.07% and 80.69% respectively. The invasion inhibition ratio of 2 mmol/L and 4 mmol/L groups of BGC-823 were 48.57% and 84.10% respectively. The expressions of c-myc and uPA significantly decreased (P < 0.05 and P < 0.01). There was no expression of c-myc in 2 mmol/L group of BGC-823. The methylation of c-myc and uPA genes in two cell lines were reversed after SAM treatment.


CONCLUSIONS
SAM can induce the apoptosis of SGC-7901 and BGC-823, block the cell cycles at G0/G1 phase and suppress the proliferation and invasion of these two cell lines. SAM can reverse the methylation of c-myc and uPA in these two cell lines and reduce their expression. SAM may act as a methyl donor to restrain the development and progression of tumor when hypomethylation is widely present in cancer.
Department of Gastroenterology, First Hospital Affiliated to Zhengzhou University, Zhengzhou 450052, China.
Ye
Y
Zhao
Jian-Sheng
JS
Li
Ming-Zhou
MZ
Guo
Bai-Sui
BS
Feng
Jin-Ping
JP
Zhang
Xiang-Yu
XY
Chen
D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019175:DNA Methylation; D016259:Genes, myc; D006801:Humans; D012436:S-Adenosylmethionine / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics
D012436:S-Adenosylmethionine; D014568:Urokinase-Type Plasminogen Activator