title: Canolol inhibits gastric tumors initiation and progression through COX-2/PGE2 pathway in K19-C2mE transgenic mice.
abstract: 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.
authors.affiliation: Division of Clinical Epidemiology, First Hospital of Jilin University, Changchun, Jilin 130021, China.
authors.forename: Donghui
authors.initials: D
authors.lastname: Cao
authors.affiliation: Division of Clinical Epidemiology, First Hospital of Jilin University, Changchun, Jilin 130021, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Diagnostic Pathology I, School of Medicine, Fujita Health University, Toyoake, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tsukamoto
authors.affiliation: Department of Gastric and Colorectal Surgery, First Hospital of Jilin University, Changchun, Jilin 130021, China.
authors.forename: Ruming
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Gastric and Colorectal Surgery, First Hospital of Jilin University, Changchun, Jilin 130021, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Ma
authors.affiliation: Division of Clinical Epidemiology, First Hospital of Jilin University, Changchun, Jilin 130021, China.
authors.forename: Zhifang
authors.initials: Z
authors.lastname: Jia
authors.affiliation: Division of Clinical Epidemiology, First Hospital of Jilin University, Changchun, Jilin 130021, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Kong
authors.affiliation: Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Oshima
authors.affiliation: Department of Gastric and Colorectal Surgery, First Hospital of Jilin University, Changchun, Jilin 130021, China.
authors.forename: Xueyuan
authors.initials: X
authors.lastname: Cao
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D015232:Dinoprostone / Q000235:genetics / Q000378:metabolism*; D053762:Interleukin-12 Subunit p40; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010636:Phenols / Q000494:pharmacology*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D014753:Vinyl Compounds / Q000494:pharmacology*
chemical_list: C587672:IL1B protein, mouse; D053762:Interleukin-12 Subunit p40; D053583:Interleukin-1beta; C549243:MIRN7 microRNA, mouse; D035683:MicroRNAs; D009363:Neoplasm Proteins; D010636:Phenols; D012334:RNA, Neoplasm; D014753:Vinyl Compounds; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D015232:Dinoprostone; C488411:4-vinyl-2,6-dimethoxyphenol