Effect of all‐trans retinoic acid on apoptosis and expression of regulatory genes (Bcl‐2, Fas,ICE) in experimentally induced gastric epithelial cell dysplasia in rats

OBJECTIVE : To study the mechanism and effect of all‐trans retinoic acid on apoptosis and the expression of Bcl‐2, Fas and ICE in experimentally induced dysplastic gastric epithelial cells. METHODS : Apoptosis and expression of Bcl‐2, Fas and ICE in gastric epithelial cells was studied using the terminal dUTP nucleotide end‐labeling (TUNEL) technique. The immunohistochemistry of Wistar rats enrolled in three groups was studied: group 1, blank controls; group 2, dysplasia induced by N‐methyl‐N‐nitro‐N‐nitrosoguanidine (MNNG) and then treated with all‐trans retinoic acid; and group 3, dysplasia induced by MNNG and treated with a placebo. RESULTS : In the three groups, the rates of dysplasia were 0, 26.7 and 73.3%; the apoptosis indices were 8.3 ± 3.1, 7.8 ± 2.6 and 2.2 ± 0.4; the expression of Bcl‐2 was 13.3, 33.3 and 66.7%; and overexpression of Bcl‐2 was 6.7, 6.7 and 33.3%, respectively. There were significant differences between group 2 and group 3 (P < 0.05), but no significant differences were found between group 2 and group 1 (P > 0.05). The expression rates of Fas were 46.7, 40 and 6.7%; the overexpression rates were 13.3, 26.7 and 13.3%, respectively; the expression rates of ICE were 20, 60 and 13.3%; the overexpression rates were 0, 13.3 and 6.7% in the three groups, respectively. The expression rates of Fas and ICE in group 2 were significantly different from that of group 3 (P < 0.05), but there were no significant differences in overexpression rates between group 2 and group 3. No significant differences were found either in expression or overexpression of Fas and ICE between group 2 and group 1. CONCLUSIONS : These results suggest that all‐trans retinoic acid inhibits Bcl‐2 expression, promotes Fas expression, enhances ICE expression and gastric mucosal epithelial cell apoptosis, and thus may reverse or inhibit the progression to cancer.