AUTHOR=He Yang , Wang Cunlong , Zhang Xiulin , Lu Xuancheng , Xing Jin , Lv Jianyi , Guo Meng , Huo Xueyun , Liu Xin , Lu Jing , Du Xiaoyan , Li Changlong , Chen Zhenwen 

TITLE=Sustained Exposure to Helicobacter pylori Lysate Inhibits Apoptosis and Autophagy of Gastric Epithelial Cells

JOURNAL=Frontiers in Oncology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.581364

DOI=10.3389/fonc.2020.581364

ISSN=2234-943X

ABSTRACT=<p><italic>Helicobacter pylori</italic> is designated as a class I carcinogen of human gastric cancer following long-term infection. During this process, <italic>H. pylori</italic> bacteria persist in proliferation and death, and release bacterial components that come into contact with gastric epithelial cells and regulate host cell function. However, the impact of long-term exposure to <italic>H. pylori</italic> lysate on the pathological changes of gastric cells is not clear. In this study, we aimed to investigate the regulation and mechanisms involved in gastric cell dysfunction following continuous exposure to <italic>H. pylori</italic> lysate. We co-cultured gastric cell lines GES-1 and MKN-45 with <italic>H. pylori</italic> lysate for 30 generations, and we found that sustained exposure to <italic>H. pylori</italic> lysate inhibited GES-1 cell invasion, migration, autophagy, and apoptosis, while it did not inhibit MKN-45 cell invasion or migration. Furthermore, Mongolian gerbils infected with <italic>H. pylori</italic> ATCC 43504 strains for 90 weeks confirmed the <italic>in vitro</italic> results. The clinical and <italic>in vitro</italic> data indicated that sustained exposure to <italic>H. pylori</italic> lysate inhibited cell apoptosis and autophagy through the <italic>Nod1-NF-κB/MAPK-ERK/FOXO4</italic> signaling pathway. In conclusion, sustained exposure to <italic>H. pylori</italic> lysate promoted proliferation of gastric epithelial cells and inhibited autophagy and apoptosis <italic>via Nod1-NF-κB/MAPK-ERK/FOXO4</italic> signaling pathway. In the process of <italic>H. pylori-</italic>induced gastric lesions, <italic>H. pylori</italic> lysate plays as an “accomplice” to carcinogenesis.</p>