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Nuclear Factor Erythroid 2-related Factor 2 Knockout Suppresses the Development of Aggressive Colorectal Cancer Formation Induced by Azoxymethane/Dextran Sulfate Sodium-Treatment in Female Mice
Colon tumors develop more frequently in male than in female. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays differential roles in the stage of tumorigenesis. The purpose of this study was to investigate the role of Nrf2 on colitis-associated tumorigenesis using Nrf2 knockout (KO) female mi...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Korean Society of Cancer Prevention
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020176/ https://www.ncbi.nlm.nih.gov/pubmed/33842405 http://dx.doi.org/10.15430/JCP.2021.26.1.41 |
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author | Song, Chin-Hee Kim, Nayoung Nam, Ryoung Hee Choi, Soo In Kang, Changhee Jang, Jae Young Nho, Heewon Shin, Eun Lee, Ha-Na |
author_facet | Song, Chin-Hee Kim, Nayoung Nam, Ryoung Hee Choi, Soo In Kang, Changhee Jang, Jae Young Nho, Heewon Shin, Eun Lee, Ha-Na |
author_sort | Song, Chin-Hee |
collection | PubMed |
description | Colon tumors develop more frequently in male than in female. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays differential roles in the stage of tumorigenesis. The purpose of this study was to investigate the role of Nrf2 on colitis-associated tumorigenesis using Nrf2 knockout (KO) female mice. Azoxymethane (AOM) and dextran sulfate sodium (DSS)-treated wild-type (WT) and Nrf2 KO female mice were sacrificed at week 2 and 16 after AOM injection. Severity of colitis, tumor incidence, and levels of inflammatory mediators were evaluated in AOM/DSS-treated WT and Nrf2 KO mice. Furthermore, qRT-PCR, Western blot abnalysis, and ELISA were performed in colon tissues. At week 2, AOM/DSS-induced colon tissue damages were significantly greater in Nrf2 KO than in WT mice. At week 16, tumor numbers (> 2 mm size) were significantly lower in both the proximal and distal colon in Nrf2 KO compared to WT. The overall incidences of adenoma/cancer of the proximal colon and submucosal invasive cancer of the distal colon were reduced by Nrf2 KO. The mRNA and protein expression levels of NF-κB-related mediators (i.e., iNOS and COX-2) and Nrf2-related antioxidants (i.e., heme oxygenase-1 and glutamate-cysteine ligase catalytic subunit) were significantly lower in the Nrf2 KO than in WT mice. Interestingly, the protein level of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) was higher in AOM/DSS-treated Nrf2 KO than in WT mice. Our results support the oncogenic effect of Nrf2 in the later stage of carcinogenesis and upregulation of tumor suppressor 15-PGDH might contribute to the repression of colitis-associated tumorigenesis in Nrf2 KO female mice. |
format | Online Article Text |
id | pubmed-8020176 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Korean Society of Cancer Prevention |
record_format | MEDLINE/PubMed |
spelling | pubmed-80201762021-04-09 Nuclear Factor Erythroid 2-related Factor 2 Knockout Suppresses the Development of Aggressive Colorectal Cancer Formation Induced by Azoxymethane/Dextran Sulfate Sodium-Treatment in Female Mice Song, Chin-Hee Kim, Nayoung Nam, Ryoung Hee Choi, Soo In Kang, Changhee Jang, Jae Young Nho, Heewon Shin, Eun Lee, Ha-Na J Cancer Prev Original Article Colon tumors develop more frequently in male than in female. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays differential roles in the stage of tumorigenesis. The purpose of this study was to investigate the role of Nrf2 on colitis-associated tumorigenesis using Nrf2 knockout (KO) female mice. Azoxymethane (AOM) and dextran sulfate sodium (DSS)-treated wild-type (WT) and Nrf2 KO female mice were sacrificed at week 2 and 16 after AOM injection. Severity of colitis, tumor incidence, and levels of inflammatory mediators were evaluated in AOM/DSS-treated WT and Nrf2 KO mice. Furthermore, qRT-PCR, Western blot abnalysis, and ELISA were performed in colon tissues. At week 2, AOM/DSS-induced colon tissue damages were significantly greater in Nrf2 KO than in WT mice. At week 16, tumor numbers (> 2 mm size) were significantly lower in both the proximal and distal colon in Nrf2 KO compared to WT. The overall incidences of adenoma/cancer of the proximal colon and submucosal invasive cancer of the distal colon were reduced by Nrf2 KO. The mRNA and protein expression levels of NF-κB-related mediators (i.e., iNOS and COX-2) and Nrf2-related antioxidants (i.e., heme oxygenase-1 and glutamate-cysteine ligase catalytic subunit) were significantly lower in the Nrf2 KO than in WT mice. Interestingly, the protein level of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) was higher in AOM/DSS-treated Nrf2 KO than in WT mice. Our results support the oncogenic effect of Nrf2 in the later stage of carcinogenesis and upregulation of tumor suppressor 15-PGDH might contribute to the repression of colitis-associated tumorigenesis in Nrf2 KO female mice. Korean Society of Cancer Prevention 2021-03-30 2021-03-30 /pmc/articles/PMC8020176/ /pubmed/33842405 http://dx.doi.org/10.15430/JCP.2021.26.1.41 Text en Copyright © 2021 Korean Society of Cancer Prevention This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Song, Chin-Hee Kim, Nayoung Nam, Ryoung Hee Choi, Soo In Kang, Changhee Jang, Jae Young Nho, Heewon Shin, Eun Lee, Ha-Na Nuclear Factor Erythroid 2-related Factor 2 Knockout Suppresses the Development of Aggressive Colorectal Cancer Formation Induced by Azoxymethane/Dextran Sulfate Sodium-Treatment in Female Mice |
title | Nuclear Factor Erythroid 2-related Factor 2 Knockout Suppresses the Development of Aggressive Colorectal Cancer Formation Induced by Azoxymethane/Dextran Sulfate Sodium-Treatment in Female Mice |
title_full | Nuclear Factor Erythroid 2-related Factor 2 Knockout Suppresses the Development of Aggressive Colorectal Cancer Formation Induced by Azoxymethane/Dextran Sulfate Sodium-Treatment in Female Mice |
title_fullStr | Nuclear Factor Erythroid 2-related Factor 2 Knockout Suppresses the Development of Aggressive Colorectal Cancer Formation Induced by Azoxymethane/Dextran Sulfate Sodium-Treatment in Female Mice |
title_full_unstemmed | Nuclear Factor Erythroid 2-related Factor 2 Knockout Suppresses the Development of Aggressive Colorectal Cancer Formation Induced by Azoxymethane/Dextran Sulfate Sodium-Treatment in Female Mice |
title_short | Nuclear Factor Erythroid 2-related Factor 2 Knockout Suppresses the Development of Aggressive Colorectal Cancer Formation Induced by Azoxymethane/Dextran Sulfate Sodium-Treatment in Female Mice |
title_sort | nuclear factor erythroid 2-related factor 2 knockout suppresses the development of aggressive colorectal cancer formation induced by azoxymethane/dextran sulfate sodium-treatment in female mice |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020176/ https://www.ncbi.nlm.nih.gov/pubmed/33842405 http://dx.doi.org/10.15430/JCP.2021.26.1.41 |
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