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

Abstract

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). 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.