Anterior gradient 2 is a novel pro-tumor factor in pancreatic cancer under NF-?B subunit RelA trans-regulation that can be suppressed by eugenic acid - 18/11/20


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Highlights |
• | Eugenic acid inhibits growth of pancreatic cancer xenograft tumors. |
• | AGR2 and NF-κB subunit RelA are elevated in pancreatic cancer. |
• | Eugenic acid represses expression of RelA and AGR2 in the xenograft tumor. |
• | Eugenic acid represses AGR2 via the NF-κB signaling. |
• | The anti-tumor action of eugenic acid was mediated by AGR2. |
Abstract |
This study aimed to examine eugenic acid (EA) as an alternative therapeutic approach against pancreatic cancer. The pancreatic cancer xenograft mouse model was employed to determine the impacts of treatment with EA on the growth of tumors. Expressions of NF-κB subunit RelA as well as Anterior gradient 2 (AGR2) were quantified in pancreatic cells treated with EA. Chromatin immunoprecipitation and luciferase report assay were performed to examine the regulation of AGR2 by RelA. The function of AGR2 as a downstream effector EA treatment was further assessed through overexpression of AGR2 in pancreatic cells. EA suppressed the growth of xenograft pancreatic tumor, and promoted the overall survival of animals with xenograft tumors. Furthermore, EA downregulated the expression of AGR2 in pancreatic cancer cells via the RelA binding site. Ectopic AGR2 overexpression attenuated the EA-elicited inhibition on the growth of xenograft pancreatic tumor, and negated the EA-induced enhancement of mouse survival. EA ameliorates pancreatic cancer through suppression of AGR2 expression, and future studies in clinical settings are needed to further assess the anti-cancer efficacy of EA.
Le texte complet de cet article est disponible en PDF.Keywords : Pancreatic cancer, Eugenic acid, NF-κB, AGR2, Xenograft
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