Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Song, Chin-Hee, Kim, Nayoung, Nam, Ryoung Hee, Choi, Soo In, Kang, Changhee, Jang, Jae Young, Nho, Heewon, Shin, Eun, Lee, Ha-Na
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Society of Cancer Prevention 2021
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
_version_ 1783674531866476544
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
work_keys_str_mv AT songchinhee nuclearfactorerythroid2relatedfactor2knockoutsuppressesthedevelopmentofaggressivecolorectalcancerformationinducedbyazoxymethanedextransulfatesodiumtreatmentinfemalemice
AT kimnayoung nuclearfactorerythroid2relatedfactor2knockoutsuppressesthedevelopmentofaggressivecolorectalcancerformationinducedbyazoxymethanedextransulfatesodiumtreatmentinfemalemice
AT namryounghee nuclearfactorerythroid2relatedfactor2knockoutsuppressesthedevelopmentofaggressivecolorectalcancerformationinducedbyazoxymethanedextransulfatesodiumtreatmentinfemalemice
AT choisooin nuclearfactorerythroid2relatedfactor2knockoutsuppressesthedevelopmentofaggressivecolorectalcancerformationinducedbyazoxymethanedextransulfatesodiumtreatmentinfemalemice
AT kangchanghee nuclearfactorerythroid2relatedfactor2knockoutsuppressesthedevelopmentofaggressivecolorectalcancerformationinducedbyazoxymethanedextransulfatesodiumtreatmentinfemalemice
AT jangjaeyoung nuclearfactorerythroid2relatedfactor2knockoutsuppressesthedevelopmentofaggressivecolorectalcancerformationinducedbyazoxymethanedextransulfatesodiumtreatmentinfemalemice
AT nhoheewon nuclearfactorerythroid2relatedfactor2knockoutsuppressesthedevelopmentofaggressivecolorectalcancerformationinducedbyazoxymethanedextransulfatesodiumtreatmentinfemalemice
AT shineun nuclearfactorerythroid2relatedfactor2knockoutsuppressesthedevelopmentofaggressivecolorectalcancerformationinducedbyazoxymethanedextransulfatesodiumtreatmentinfemalemice
AT leehana nuclearfactorerythroid2relatedfactor2knockoutsuppressesthedevelopmentofaggressivecolorectalcancerformationinducedbyazoxymethanedextransulfatesodiumtreatmentinfemalemice