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| Signaling Pathway by DT-3 a Inhibitor of the PKGIα Pathway on Proliferation and Migration of Gastric Cancer Cells |
| ZHANG Xiufen, et al |
| The Affiliated Hospital of Chengde Medical University, Hebei Chengde 067000, China |
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Abstract Objective: To investigate the effect of DT-3, a specific inhibitor of the PKGIα signaling pathway, on the proliferation and migration of gastric cancer cells. Methods: Bioinformatics analysis was used to analyze the differential expression of PKGI in tissues and explore the prognosis of PKGI and PKGIα in gastric cancer patients based on the GEO, TCGA, HPA, Kaplan-Meier plotter databases and GEPIA online analysis website. CCK-8 and colony formation assays were used to detect the effect of DT-3 on cell proliferation, and wound healing assay was used to observe the effect of DT-3 on cell migration. Western blotting was used to verify the protein expression of PKGIα and correlation analysis was performed. Results: The expression of PKGI mRNA was increased in gastric adenocarcinoma tissues, and 27 out of 42 gastric cancer cell lines expressed PKGI mRNA. Gastric cancer tissues with high expression of PKGIα mRNA were more aggressive. Immunohistochemical (IHC) results showed that 6 out of 12 gastric cancer tissues showed moderate to strong cytoplasmic positive staining reaction. The expression of PKGI was negatively correlated with CDH1 (r=-0.74, P<0.05). Survival analysis showed that high expression of PKGI and PKGIα mRNA was significantly associated with overall survival (OS) of gastric adenocarcinoma patients (HR>1, logrank P<0.05). The experimental results showed that the expression of PKGIα protein was increased in human gastric cancer cell line AGS. DT-3 inhibited cell proliferation and migration (P<0.05), decreased the expression of phosphorylated p65 of NF-κB, and the expression of PKGI and NF-κB p-p65 was extremely positively correlated (r=0.957, P<0.05). Conclusion: Inhibition of the PKGIα signaling pathway by DT-3 can effectively inhibit the proliferation and migration of gastric cancer cells.
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2024, Vol. 30 
