Trefoil factor 1 and gastrokine 2 inhibit Helicobacter pylori-induced proliferation and inflammation in gastric cardia and distal carcinogenesis.

Helicobacter pylori (H. pylori) infection has been associated with non-cardia adenocarcinoma in the stomach, while its role in gastric cardia adenocarcinoma (GCA) remains controversial. In addition, the association between H. pylori and the protective factors trefoil factor 1 (TFF1) and gastrokine 2 (GKN2) in gastroesophageal adenocarcinomas has not been fully investigated. Therefore, the mRNA and protein expression levels of TFF1 and GKN2 in GCA and distal gastric adenocarcinoma (DGA) were analyzed using quantitative PCR (qPCR) and immunohistochemistry, and the association with H. pylori infection was investigated. In addition, the effects of TFF1 and GKN2 overexpression on H. pylori-induced cells were investigated using western blot and reverse transcription-qPCR analysis. The comparative analysis of 16S rRNA-positive mRNA expression between GCA and DGA showed no statistically significant difference. However, the rate of the H. pylori vacuolating toxin A (VacA) genotype was significantly higher in GCA (49.2%) compared with that in DGA (26.9%; P<0.05). H. pylori infection downregulated the mRNA and protein expression levels of TFF1 and GKN2 in gastric tumor tissues, and the mRNA expression level of TFF1 and GKN2 was also markedly decreased in vitro. Furthermore, the cell proliferation varied in H. pylori total protein treatment group with the different doses. Notably, treatment with 20 µg/ml H. pylori total protein for 24 h resulted in the highest cellular proliferation rate. In addition, TFF1 and GKN2 overexpression inversely inhibited H. pylori-induced cell proliferation and upregulated NF-κB, tumor necrosis factor-α, IL-1β, IL-2, IL-4 and IL-6. The results of the present study indicate that H. pylori, particularly the VacA+ strain, plays an important role in GCA pathogenesis in high-risk areas of China, while TFF1/GKN2 inhibits H. pylori-induced cell proliferation and inflammation in GCA and DGA. [ABSTRACT FROM AUTHOR]