P2X7 receptor promotes the growth and metastasis of gastric cancer by activating P13/AKT/GSK-3 beta signaling (experimental research)
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View abstract on PubMed
Summary
This summary is machine-generated.Activation of the P2X7 receptor (P2X7R) promotes gastric cancer (GC) proliferation and metastasis by activating PI3K/AKT/GSK-3beta signaling. P2X7R represents a potential therapeutic target for gastric cancer treatment.
Area Of Science
- Oncology
- Molecular Biology
- Cell Biology
Background
- Gastric cancer (GC) remains a significant global health challenge.
- Understanding the molecular mechanisms driving GC progression is crucial for developing effective treatments.
Purpose Of The Study
- To investigate the role of the P2X7 receptor (P2X7R) in gastric cancer (GC) cell proliferation and metastasis.
- To elucidate the underlying molecular mechanisms, including signaling pathways involved in P2X7R-mediated GC progression.
Main Methods
- In vitro studies using GC cell lines (AGS, HGC-27) to assess calcium influx, cell proliferation, migration, and invasion.
- In vivo experiments in animal models to evaluate the effect of P2X7R activation on tumor growth.
- Analysis of gene and protein expression related to epithelial-mesenchymal transition (EMT) and metastasis.
- Pharmacological inhibition and genetic silencing (siP2X7R) of P2X7R function.
Main Results
- P2X7R activation by ATP/BzATP increased calcium influx and promoted GC cell proliferation, migration, and invasion.
- P2X7R activation enhanced actin fiber stability and altered cell morphology.
- P2X7R activation upregulated EMT/metastasis markers (MMP-2, MMP-9, N-cadherin, Zeb1, Vimentin, Snail) and downregulated E-cadherin.
- Inhibition or silencing of P2X7R reversed these effects.
- P2X7R activation led to the activation of the PI3K/AKT/GSK-3beta signaling pathway.
- In vivo studies confirmed that P2X7R activation promotes tumor growth.
Conclusions
- P2X7R activation significantly promotes gastric cancer cell proliferation, metastasis, and EMT.
- The PI3K/AKT/GSK-3beta signaling pathway is a key mediator of P2X7R's pro-tumorigenic effects in GC.
- P2X7R emerges as a promising therapeutic target for gastric cancer treatment.
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