Effects of folic acid on epithelial apoptosis and expression of Bcl-2 and p53 in premalignant gastric lesions.
OBJECTIVE
To evaluate the effects of folic acid on epithelial apoptosis and expression of Bcl-2 and p53 in the tissues of premalignant gastric lesions.


METHODS
Thirty-eight patients, with premalignant gastric lesions including 18 colonic-type intestinal metaplasia (IM) and 20 mild or moderate dysplasia, were randomly divided into a treatment group (n = 19) receiving folic acid 10 mg thrice daily and a control group (n = 19) receiving sucralfate 1,000 mg thrice daily for 3 mo. All patients underwent endoscopies and four biopsies were taken prior to treatment and repeated after concluding therapy. Folate concentrations in gastric mucosa were measured with chemiluminescent enzyme immunoassay. Epithelial apoptosis and the expression of Bcl-2 and p53 protein in gastric mucosa were detected with flow cytometric assay.


RESULTS
The mean of folate concentration in gastric mucosa was 9.03+/-3.37 microg/g wet wt in the folic acid treatment group, which was significantly higher than 6.83+/-3.02 microg/g wet wt in the control group. Both the epithelial apoptosis rate and the tumor suppressor p53 expression in gastric mucosa significantly increased after folic acid treatment. In contrast, the expression of Bcl-2 oncogene protein decreased after folic acid therapy.


CONCLUSIONS
These data indicate that folic acid may play an important role in the chemoprevention of gastric carcinogenesis by enhancing gastric epithelial apoptosis in the patients with premalignant lesions.
Cao
Da-Zhong
DZ
Department of Gastroenterology, Zhongda Hospital of Southeast University, Nanjing 210009, Jiangsu Province, China.
Sun
Wei-Hao
WH
Ou
Xi-Long
XL
Yu
Qian
Q
Yu
Ting
T
Zhang
You-Zhen
YZ
Wu
Zi-Ying
ZY
Xue
Qi-Ping
QP
Cheng
Yun-Lin
YL
D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D016193:G1 Phase / Q000187:drug effects; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D006397:Hematinics / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011230:Precancerous Conditions / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D006397:Hematinics; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D005492:Folic Acid