4-Vinyl-2, 6-dimethoxyphenol (
canolol) is an
antioxidant phenolic compound extracted from crude
canola oil. In current research, K19-C2mE transgenic mice, developing hyperplastic
tumors spontaneously in the glandular stomach, were used to study the mechanisms involved in the anti-
inflammation and anti-
tumor effects of
canolol. Tg mice receiving
canolol diet had a reduced
tumor incidence, to 41.2%, compared with Non-treatment Tg mice, 77.8% of which had gastric
tumor (P=0.002). Besides that, the mean
tumor diameter was decreased from 6.5 mm to 4.5 mm (P<0.001) after
canolol administration. COX-2/
PGE2 pathway is known to play pivotal role in
inflammation-induced gastric
tumorigenesis. The neutrophils and lymphocytes infiltration was suppressed significantly, and the
mRNA levels of the proinflammatory
cytokines COX-2, IL-1β and IL-12b were also downregulated in gastric mucosa. Additionally, immunohistochemical analysis showed that COX-2, EP2, Gαs and β-
catenin, key factors involving in
PGE2 signal transduction, were positive staining with higher H scores in Non-treatment Tg mice, while the expressions were suppressed significantly by 0.1%
canolol (P<0.001). In addition,
tumor-suppressor miR-7 was reactivated after
canolol administration, and COX-2 was showed to be a functional target of miR-7 to suppress the
tumor progression. In conclusion,
canolol could inhibit the
gastritis-related
tumor initiation and progression, and the suppression effect was correlated with the blocking up of canonical COX-2/
PGE2 signaling pathway and might be regulated by miR-7.