Gankyrin Inhibition Can Control Helicobacter pylori Generated Gastric Cancer Using In Vivo Xenograft Models

Abstract

Background

Gastric cancer (GC) is a leading cause of cancer-related mortality worldwide, with Helicobacter pylori (H. pylori) infection recognized as a significant risk factor. H. pylori infects approximately 50% of the global population, contributing to chronic gastritis, peptic ulcers, and the development of GC. The oncoprotein Gankyrin (PSMD10) has been implicated in various human cancers, including hepatocellular carcinoma, gastric cancer, and lung cancer, by modulating autophagy and inflammatory pathways.

Methods

In this study, we explored the role of Gankyrin in H. pylori-induced gastric tumorigenesis via a Swiss albino mouse xenograft model. Mice were subcutaneously injected with H. pylori-infected AGS cells with or without Gankyrin knockdown.

Results

We assessed tumor growth and inflammatory markers (TNF-α and IL-6) levels and Gankyrin's downstream signaling molecules (p53, pRb, and NF-κB). Our results demonstrated that Gankyrin knockdown significantly decreased tumor formation in Swiss albino mice engrafted with H. Pylori-infected AGS cells. Notably, treatment with cyclosporine A significantly decreased the expression of TNF-α in all the AGS-engrafted mice except the PBS group. Moreover, our results show that the downregulation of Gankyrin significantly elevated the expression of NF-κB, pRb, and p53.

Conclusion

These findings suggest that Gankyrin plays a crucial role in H. pylori-mediated GC progression by modulating inflammatory and tumor suppressor pathways. Targeting Gankyrin could provide a therapeutic strategy to mitigate the development of GC associated with H. pylori infection.