Hypoxia and Hypoxia‐Reoxygenation Potentiate Helicobacter pylori Infection and Gastric Epithelial Cell Proliferation

作者：Indrajit Poirah, S.P. Chakraborty, Pratyush Kumar Padhan, Ashish Kumar Mishra, Debashish Chakraborty, Pragyesh Dixit, Supriya Samal, Niranjan Rout, Shivaram Prasad Singh, Gautam Nath, Duane T. Smoot, Hassan Ashktorab, Asima Bhattacharyya · 发表于：Cancer Medicine · 年份：2025 · DOI：10.1002/cam4.70860 · 被引用次数：3 · 研究领域：Radiopharmaceutical Chemistry and Applications、Helicobacter pylori-related gastroenterology studies、Cancer, Stress, Anesthesia, and Immune Response

INTRODUCTION: The gastric epithelium experiences intermittent hypoxia due to various physiological and pathological conditions. However, the impact of hypoxia and hypoxia-reoxygenation of gastric epithelial cells (GECs) on Helicobacter pylori-mediated gastric cancer (GC) has never been investigated. Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) facilitate H. pylori adhesion onto GECs. We evaluated the effect of hypoxia and hypoxia-reoxygenation on CEACAM6-mediated H. pylori binding, infection, reactive oxygen species (ROS) generation, and GEC proliferation. METHODS: Hypoxia-inducible factor 1 (HIF1α) and CEACAM6 levels were assessed in various GECs. ROS were measured using 2',7'-dichlorofluorescin diacetate (DCFDA). Bioinformatics analyses were performed to identify the most prominent stomach adenocarcinoma (STAD)-associated NADPH oxidase (NOX) followed by validation by overexpression/suppression studies and western blotting. GC biopsies were examined by immunofluorescence microscopy. Hypoxia-exposed, reoxygenated, or control cells were compared for ROS generation and H. pylori infection. MTT assay determined cell proliferation. RESULTS AND CONCLUSIONS: Hypoxia and HIF1 mediated upregulation of CEACAM6 in GECs. CEACAM6 significantly promoted ROS generation by inducing NOX4 in hypoxic GECs. HIF1α, CEACAM6, and NOX4 upregulation was detected in gastritis and GC tissues. H. pylori infection significantly increased in hypoxia-exposed GECs as compared to normo...