1. Academic Validation
  2. Chloroquine inhibited Helicobacter pylori-related gastric carcinogenesis by YAP-β-catenin-autophagy axis

Chloroquine inhibited Helicobacter pylori-related gastric carcinogenesis by YAP-β-catenin-autophagy axis

  • Microb Pathog. 2023 Oct 11:184:106388. doi: 10.1016/j.micpath.2023.106388.
Boqing Li 1 Yunqiu Du 2 Jing He 1 Xin Lv 1 Sisi Liu 1 Xiaolin Zhang 1 Ying Zhang 3
Affiliations

Affiliations

  • 1 School of Basic Medical Sciences, Binzhou Medical University, Yantai, 264003, China.
  • 2 Department of Prenatal Diagnosis, Lianyungang Maternal and Child Health Hospital, Lianyungang, Jiangsu, 222000, China.
  • 3 School of Basic Medical Sciences, Binzhou Medical University, Yantai, 264003, China. Electronic address: zhangying@bzmc.edu.cn.
Abstract

YAP participates in Autophagy associated with many diseases. In this study, we demonstrate that YAP promotes Autophagy by interacting with beclin 1, upregulating beclin 1 and LC3B-II protein expression, and promoting autophagosome formation after H. pylori Infection in a vacuolating cytotoxin A-dependent manner. The protein levels of β-catenin in the cytoplasm and nuclei of GES-1 cells and the mRNA levels of Axin2, Myc, Lgr5, and Ccnd1 were increased in H. pylori-infected cells or YAP-overexpressed cells, but were decreased in YAP-silenced cells. The β-catenin Inhibitor XAV939 significantly downregulated Autophagy, whereas the activator LiCl showed opposite effects. An H. pylori-infected mouse model of gastric carcinoma was successfully established. The mouse model showed that H. pylori Infection, when combined with NMU, promoted the tumorigenesis of gastric tissues; increased IL-1β, IL-6, and TNF-α levels; promoted NO release; and increased the expression of beclin 1, LC3B-II more than NMU alone. Chloroquine inhibited these phenomena, but did not completely attenuate the effects of H. pylori. These results demonstrate that chloroquine can be used as a drug for the treatment of H. pylori-related gastric Cancer, but the treatment should simultaneously remove H. pylori.

Keywords

Autophagy; Helicobacter pylori; Vacuolating cytotoxin A; Yes associated transcriptional regulator; β-catenin.

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