Chronic restraint stress promotes gastric epithelial malignant transformation by activating the Akt/p53 signaling pathway via ADRB2

The etiology of gastric cancer is associated with infectious, environmental and dietary factors, as well as genetic background. Additionally, emerging evidence has supported the vital role of chronic emotional stress on gastric carcinogenesis; however, the underlying mechanism remains unclear. The p...

Descripción completa

Detalles Bibliográficos
Autores principales: Zong, Chuanju, Yang, Maoquan, Guo, Xiaojing, Ji, Wansheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353258/
https://www.ncbi.nlm.nih.gov/pubmed/35949623
http://dx.doi.org/10.3892/ol.2022.13420
_version_ 1784762836168212480
author Zong, Chuanju
Yang, Maoquan
Guo, Xiaojing
Ji, Wansheng
author_facet Zong, Chuanju
Yang, Maoquan
Guo, Xiaojing
Ji, Wansheng
author_sort Zong, Chuanju
collection PubMed
description The etiology of gastric cancer is associated with infectious, environmental and dietary factors, as well as genetic background. Additionally, emerging evidence has supported the vital role of chronic emotional stress on gastric carcinogenesis; however, the underlying mechanism remains unclear. The present study aimed to investigate the effects of chronic stress and a detrimental diet on gastric malignant epithelial transformation in rats. Therefore, 26 Wistar rats were randomly divided into the following four groups: i) Control; ii) detrimental diet (DD); iii) detrimental diet with chronic restraint (DR) and iv) detrimental diet with chronic restraint and propranolol treatment (DRP). ELISA was performed to detect the serum levels of epinephrine and norepinephrine. Epithelial cell apoptosis was analyzed using the TUNEL assay. The mRNA and protein expression levels of Akt and p53 were detected using reverse transcription quantitative PCR and western blotting, respectively. Pathological changes were analyzed using hematoxylin and eosin staining (H&E). The H&E staining results showed that dysplasia in the gastric mucosa occurred in two of eight rats in the DD group and in four of five rats in the DR group, whereas no dysplasia was detected in the DRP group. The apoptotic ratios of gastric epithelial cells were significantly decreased in all treatment groups compared with the control group. Adrenoceptor β2 (ADRB2) protein expression levels were increased significantly only in the DR group and this effect was significantly reduced in the DRP group. The mRNA expression levels of Akt and p53 were significantly upregulated in the DD group, and Akt mRNA expression was further elevated in the DR group. With regard to protein expression, the levels of Akt and p-Akt were significantly increased in the DR group, whereas these effects were reversed in the DRP group. Furthermore, the ratio of p-p53/p53 protein was significantly reduced in the DD or DR groups, but was reversed in the DRP group. Collectively, the findings of the present study suggested that chronic restraint stress potentially aggravates the gastric epithelial malignant transformation induced by a detrimental diet, at least partially via the Akt/p53 signaling pathway mediated via ADRB2.
format Online
Article
Text
id pubmed-9353258
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher D.A. Spandidos
record_format MEDLINE/PubMed
spelling pubmed-93532582022-08-09 Chronic restraint stress promotes gastric epithelial malignant transformation by activating the Akt/p53 signaling pathway via ADRB2 Zong, Chuanju Yang, Maoquan Guo, Xiaojing Ji, Wansheng Oncol Lett Articles The etiology of gastric cancer is associated with infectious, environmental and dietary factors, as well as genetic background. Additionally, emerging evidence has supported the vital role of chronic emotional stress on gastric carcinogenesis; however, the underlying mechanism remains unclear. The present study aimed to investigate the effects of chronic stress and a detrimental diet on gastric malignant epithelial transformation in rats. Therefore, 26 Wistar rats were randomly divided into the following four groups: i) Control; ii) detrimental diet (DD); iii) detrimental diet with chronic restraint (DR) and iv) detrimental diet with chronic restraint and propranolol treatment (DRP). ELISA was performed to detect the serum levels of epinephrine and norepinephrine. Epithelial cell apoptosis was analyzed using the TUNEL assay. The mRNA and protein expression levels of Akt and p53 were detected using reverse transcription quantitative PCR and western blotting, respectively. Pathological changes were analyzed using hematoxylin and eosin staining (H&E). The H&E staining results showed that dysplasia in the gastric mucosa occurred in two of eight rats in the DD group and in four of five rats in the DR group, whereas no dysplasia was detected in the DRP group. The apoptotic ratios of gastric epithelial cells were significantly decreased in all treatment groups compared with the control group. Adrenoceptor β2 (ADRB2) protein expression levels were increased significantly only in the DR group and this effect was significantly reduced in the DRP group. The mRNA expression levels of Akt and p53 were significantly upregulated in the DD group, and Akt mRNA expression was further elevated in the DR group. With regard to protein expression, the levels of Akt and p-Akt were significantly increased in the DR group, whereas these effects were reversed in the DRP group. Furthermore, the ratio of p-p53/p53 protein was significantly reduced in the DD or DR groups, but was reversed in the DRP group. Collectively, the findings of the present study suggested that chronic restraint stress potentially aggravates the gastric epithelial malignant transformation induced by a detrimental diet, at least partially via the Akt/p53 signaling pathway mediated via ADRB2. D.A. Spandidos 2022-07-05 /pmc/articles/PMC9353258/ /pubmed/35949623 http://dx.doi.org/10.3892/ol.2022.13420 Text en Copyright: © Zong et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Zong, Chuanju
Yang, Maoquan
Guo, Xiaojing
Ji, Wansheng
Chronic restraint stress promotes gastric epithelial malignant transformation by activating the Akt/p53 signaling pathway via ADRB2
title Chronic restraint stress promotes gastric epithelial malignant transformation by activating the Akt/p53 signaling pathway via ADRB2
title_full Chronic restraint stress promotes gastric epithelial malignant transformation by activating the Akt/p53 signaling pathway via ADRB2
title_fullStr Chronic restraint stress promotes gastric epithelial malignant transformation by activating the Akt/p53 signaling pathway via ADRB2
title_full_unstemmed Chronic restraint stress promotes gastric epithelial malignant transformation by activating the Akt/p53 signaling pathway via ADRB2
title_short Chronic restraint stress promotes gastric epithelial malignant transformation by activating the Akt/p53 signaling pathway via ADRB2
title_sort chronic restraint stress promotes gastric epithelial malignant transformation by activating the akt/p53 signaling pathway via adrb2
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353258/
https://www.ncbi.nlm.nih.gov/pubmed/35949623
http://dx.doi.org/10.3892/ol.2022.13420
work_keys_str_mv AT zongchuanju chronicrestraintstresspromotesgastricepithelialmalignanttransformationbyactivatingtheaktp53signalingpathwayviaadrb2
AT yangmaoquan chronicrestraintstresspromotesgastricepithelialmalignanttransformationbyactivatingtheaktp53signalingpathwayviaadrb2
AT guoxiaojing chronicrestraintstresspromotesgastricepithelialmalignanttransformationbyactivatingtheaktp53signalingpathwayviaadrb2
AT jiwansheng chronicrestraintstresspromotesgastricepithelialmalignanttransformationbyactivatingtheaktp53signalingpathwayviaadrb2