Signaling Pathway by DT-3 a Inhibitor of the PKGIα Pathway on Proliferation and Migration of Gastric Cancer Cells
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 gas-tric cancer patients based on the GEO,TCGA,HPA,Kaplan-Meier plotter databases and GEPIA online a-nalysis website.CCK-8 and colony formation assays were used to detect the effect of DT-3 on cell prolifera-tion,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 ex-pressed PKGI mRNA.Gastric cancer tissues with high expression of PKGIα mRNA were more aggressive.Im-munohistochemical(IHC)results showed that 6 out of 12 gastric cancer tissues showed moderate to strong cy-toplasmic 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 associ-ated with overall survival(OS)of gastric adenocarcinoma patients(HR>1,logrank P<0.05).The experi-mental 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.
PKGIα pathwayDT-3NF-κB p-p65Bioinformatics analysisGastric cancer cell AGS
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