Autophagy induced by H. pylori VacA regulated the survival mechanism of the SGC7901 human gastric cancer cell line

Abstract

Background Vacuolating cytotoxin (VacA) is an important virulence factor of Helicobacter pylori (H. pylori). It was previously believed that VacA can trigger the cascade of apoptosis on mitochondria to lead to cell apoptosis. Recently, it was found that VacA can induce autophagy. However, the molecular mechanism by which VacA induces autophagy is largely unknown. Objective We aimed to explore the molecular mechanism of autophagy induced by H. pylori in gastric cancer cells and the effect of autophagy on the survival of gastric cancer cells. Methods The autophagy of human gastric cancer cell line SGC7901 was detected by Western blot and RT-PCR in the treatment of VacA protein of H. pylori. The relationship between autophagy and reactive oxygen species (ROS) in the proliferation of gastric cancer cells were studied by gene expression silences (siRNA) and CM-H2DCFDA (DCF) staining. Results The results showed that VacA protein secreted by H. pylori in the supernatant stimulated autophagy in SGC7901 cells. After VacA protein treatment, the mRNA expressions of BECN1, ATG7 and PIK3C3, were up-regulated. ATG7 silencing by siRNA inhibited VacA-induced autophagy. Furthermore, our data demonstrated that VacA protein increased ROS levels. Addition of the antioxidant N-acetyl-l-cysteine (NAC) suppressed the levels of ROS, leading to inhibition of autophagy. Conclusions H. pylori VacA is a key toxin that induces autophagy by increased ROS levels. And our findings demonstrated that VacA significantly inhibited proliferation in SGC7901 cells.

Vacuolating Cytotoxin A Triggers Mitophagy in Helicobacter pylori-Infected Human Gastric Epithelium Cells

“…The mechanisms underlying autophagy induction by H. pylori or HPCF are complex ( 21 ). Two virulence factors, vacuolating cytotoxin (VacA) and cytotoxin-associated gene A (CagA), play very important roles in autophagy ( 21 – 23 , 34 , 41 , 42 ). Considering plenty of studies have shown that VacA can damage mitochondria and destroy the mitochondrial membrane potential (MMP), the first event we wanted to know was whether mitophagy is involved ( 43 , 44 ).…”

Reactive Oxygen Species and H. pylori Infection: A Comprehensive Review of Their Roles in Gastric Cancer Development

“…Pan Zhu et al reported that VacA could induce autophagy and increase cell death via numerous dilated numerous endoplasmic reticula (ER), increase the eukaryotic translation initiation factor 2 subunit 1 phosphorylation, and also increase expression of tribbles pseudokinase homolog 3 (TRIB3) upon ER stress in AGS cells [ 133 ]. Similarly, increased ROS levels and BECN1, ATG7, and PIK3C3 mRNA expressions were observed following VacA protein treatment in SGC7901 cells, which facilitated a significant decrease in proliferation and an increase in autophagy [ 134 ]. Studies have also shown that CagA and VacA can inhibit autophagy signaling upstream along with autophagy-lysosome maturation, inhibiting gastric autophagy in precancerous lesions of GC.…”

Helicobacter pylori-Mediated Oxidative Stress and Gastric Diseases: A Review

“…In addition, it affects the cell migration and differentiation of the GHCs ( Bussière et al, 2005 ). Recent studies have indicated that VacA, a key toxin of inducing autophagy and apoptosis, can be considered as a marker to predict the risk of gastric carcinogenesis in animal models ( Carlosama-Rosero et al, 2021 ; Luo et al, 2021 ).…”