Effect and mechanism of N-acetylcysteine on methylnitrosourea-induced precancerous lesions of gastric cancer

DING Xiaorui; LU Minmin; DONG Hao

doi:10.7619/jcmp.20245014

Journal of Clinical Medicine in Practice > 2025 > 29(2): 6-13. > DOI: 10.7619/jcmp.20245014

DING Xiaorui, LU Minmin, DONG Hao. Effect and mechanism of N-acetylcysteine on methylnitrosourea-induced precancerous lesions of gastric cancer[J]. Journal of Clinical Medicine in Practice, 2025, 29(2): 6-13. DOI: 10.7619/jcmp.20245014

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Effect and mechanism of N-acetylcysteine on methylnitrosourea-induced precancerous lesions of gastric cancer

Department of Gastroenterology, Binzhou People's Hospital of Shandong Province, Binzhou, Shandong, 256610

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Received Date: October 21, 2024
Revised Date: December 24, 2024

Graphical Abstract

Abstract

Abstract

Objective
To investigate the effects of N-acetylcysteine (NAC) on methylnitrosourea (MNNG)-induced precancerous lesions of gastric cancer (PLGC) and analyze its underlying mechanisms.
Methods
Gastric epithelial cell line GES-1 was cultured in vitro and treated with different concentrations of MNNG. The rat PLGC model was established by MNNG induction. The morphological changes of the cells were observed by microscope, and the migration and invasion ability of the cells were evaluated by wound healing and transwell tests, respectively. Western blot analysis was conducted to evaluate epithelial-mesenchymal transition (E-cadherin and N-cadherin proteins expression) and related proteins expression of reactive oxygen species (ROS)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/nuclear factor-κB (NF-κB) pathway [phosphorylated PI3K (p-PI3K), p-AKT and nuclear p65 protein]. ROS levels were detected using DCFH-DA staining. Histopathological changes in gastric tissues were observed using hematoxylin and eosin (HE) staining.
Results
In vitro experiments demonstrated that NAC treatment alleviated MNNG-induced alterations in the morphology and growth characteristics of GES-1 cells, inhibiting cell migration and invasion. In vitro experiments showed that NAC treatment reduced MNNG-induced lesions and hyperplasia. NAC inhibited the EMT process (increased E-cadherin expression and decreased N-cadherin expression) and suppressed the ROS/PI3K/AKT/NF-κB pathway (decreased expression of p-PI3K, p-AKT and nuclear p65 protein) both in vitro and in vivo. Activation of the ROS/PI3K/AKT/NF-κB pathway partially reversed the effects of NAC on MNNG-induced cell migration, invasion, epithelial-mesenchymal transition and related proteins in the ROS/PI3K/AKT/NF-κB pathway in GES-1 cells.
Conclusion
The protective effect of NAC on MNNG-induced PLGC may be associated with the inactivation of the ROS/PI3K/AKT/NF-κB pathway.

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References (26)

References

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Effect and mechanism of N-acetylcysteine on methylnitrosourea-induced precancerous lesions of gastric cancer