The effects of CEACAM19 on the proliferation,pyroptosis,and invasion of gastric cancer cells via modulation of the AMPK/SIRT1/NF-κB signaling pathway
ZHAO Hongying
JIANG Rongke
LI Yanfang
ZHU Mei
ZHANG Guihua
WANG Yu
CAO Shengya
Abstract：Objective To investigate the effects of carcinoembryonic antigen-related cell adhesion molecule 19(CEACAM19)on the proliferation,pyroptosis,and invasion of human gastric cancer cells via modulation of the adenosine monophosphate activated protein kinase(AMPK)/silent information regulator two homolog 1(SIRT1)/nuclear factor kappa B(NF-κB)signaling pathway.Methods The gastric adenocarcinoma cell line AGS was selected and divided into the following groups:Control group(non-transfected with plasmid),siRNA-NC group(transfected with CEACAM19 negative control),si-Cc19 group(transfected with CEACAM19 siRNA),si-Cc1 9+DMSO group(treated with DMSO after CEACAM19 siRNA transfection),and si-Cc1 9+AMPK inhibitor Compound C group(treated with Compound C after CEACAM19 siRNA transfection).Cell proliferation was assessed using the cell counting kit-8(CCK-8)assay and colony formation experiments.Cell pyroptosis was observed via scanning electron microscopy.Cell invasion capability was evaluated using the Transwell assay.Western blot was employed to detect the expression levels of proteins related to gasdermin D(GSDMD),cysteine aspartate-specific protease-1(caspase-1),E-cadherin,N-cadherin,and proteins related to the AMPK/SIRT1/NF-κB signaling pathway(AMPK,p-AMPK,SIRT1,p65,p-p65).Results Compared with the siRNA-NC group,the si-Cc19 group showed significantly decreased AGS cell survival rate,colony formation rate,number of invasive cells,N-cadherin expression,and p-p65/p65 ratio(P＜0.05),while the expression levels of pyroptosis-related proteins(GSDMD,caspase-1,E-cadherin)and pathway-related proteins(p-AMPK/AMPK/SIRT1)as well as interleukin-18(IL-18)in cell supernatant were significantly elevated(P＜0.05).Scanning electron microscopy results revealed that more AGS cells in the si-Cc1 9 group underwent swelling and rupture,with small pores appearing on the cell surface.In contrast,the si-Cc19+Compound C group showed significantly increased colony formation rate,cell survival rate,cell invasion count,p-p65/p65,and N-cadherin levels(P＜0.05),while the expression levels of GSDMD,caspase-1,E-cadherin,p-AMPK/AMPK,SIRT1,and IL-18 in cell supernatant were significantly decreased(P＜0.05),with reduced cell swelling and rupture.Conclusion CEACAM19 may promote the proliferation and invasion of gastric cancer cells and inhibit cell pyroptosis by regulating the AMPK/SIRT1/NF-κB signaling pathway.
Keywords：gastric cancercarcinoembryonic antigen-related cell adhesion molecule 19adenosine monophosphate activated protein kinase/silent information regulator two homolog 1/nuclear factor kappa B signaling pathway
Publication Date：2026-02-28
Online Publishing Date：2026-04-01(First online date of this platform, not the publication date of the document)
Pages：6( 121-126 )