Browse

Effect of estradiol in an azoxymethane/dextran sulfate sodium-treated mouse model of colorectal cancer: Implication for sex difference in colorectal cancer development

Cited 17 time in Web of Science Cited 14 time in Scopus
Authors
Son, Hee Jin; Sohn, Sung Hwa; Kim, Nayoung; Lee, Ha-Na; Lee, Sun Min; Nam, Ryoung Hee; Park, Ji Hyun; Song, Chin-Hee; Shin, Eun; Na, Hee Young; Kim, Joo Sung; Lee, Dong Ho; Surh, Young-Joon
Issue Date
2019-04
Citation
Cancer Research and Treatment, Vol.51 No.2, pp.632-648
Keywords
Colorectal neoplasmsAOM/DSS mouse modelEstradiolNF-kappa BNF-E2-related factor 2Nod-like receptor protein 3 inflammasomeMouse
Abstract
Purpose This study demonstrates that estradiol downregulates inflammation and inhibits colorectal cancer (CRC) development in azoxymethane/dextran sulfate sodium (AOM/DSS) mouse model. Materials and Methods AOM/DSS-treated male and female mice were sacrificed at weeks 2, 10, and 16, to assess estrogen effects on colitis and carcinogenesis. Macroscopic and histologic severity of colitis and Western blot and quantitative real-time polymerase chain reaction were evaluated, to measure inflammatory mediators and cytokines. Results Compared with AOM/DSS-treated male mice (M-AOM/DSS group), AOM/DSS-treated male mice with estradiol administration (M-AOM/DSS+ estr group) displayed at week 2 significantly decreased severity of colitis. At weeks 10 and 16, AOM/DSS-treated female mice (F-AOM/DSS group) and the M-AOM/DSS+ estr group showed significantly lower tumor multiplicity compared with the M-AOM/DSS group. At week 2, F-AOM/DSS group had a lower level of nuclear factor-. B (NF-. B) expression and higher level of nuclear factor erythroid 2-related factor 2 (Nrf2) expression, compared to the M-AOM/DSS group. At week 2, expression levels of NF-. B and its related mediators decreased in the M-AOM/DSS+ estr group, while levels of Nrf2 and Nrf2-related anti-oxidant enzymes increased. In addition, estradiol significantly increased Nod-like receptor protein 3 (NLRP3) inflammasome expressions in AOM/DSS-treated male mice. In contrast, at weeks 10 and 16, Nrf2 and its-related anti-oxidant enzymes and NLRP3 inflammasome were highly expressed in M-AOM/DSS group and in F-AOM/DSS group, who developed cancer. Conclusion The data suggest that estradiol inhibits the initiation of CRC by regulating Nrf2-related pathways. Moreover, these imply the dual role of Nrf2 and NLRP3 inflammasome, including promotion of tumor progression upon tumor initiation.
ISSN
1598-2998
URI
https://hdl.handle.net/10371/172601
DOI
https://doi.org/10.4143/crt.2018.060
Files in This Item:
There are no files associated with this item.
Appears in Collections:
Graduate School of Convergence Science and Technology (융합과학기술대학원)Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과)Journal Papers (저널논문_분자의학 및 바이오제약학과)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse