Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/26677
Title: Captopril, a Renin-Angiotensin System Inhibitor, Attenuates Features of Tumor Invasion and Down-Regulates C-Myc Expression in a Mouse Model of Colorectal Cancer Liver Metastasis.
Austin Authors: Riddiough, Georgina E ;Fifis, Theodora;Walsh, Katrina A;Muralidharan, Vijayaragavan ;Christophi, Christopher ;Tran, Bang M;Vincan, Elizabeth;Perini, Marcos V 
Affiliation: Surgery (University of Melbourne)
Curtin Medical School, Curtin University, Perth, WA 6102, Australia
Victorian Infectious Diseases Reference Laboratory, The Peter Doherty Institute, Melbourne, VIC 3000, Australia
Department of Infectious Diseases, The Peter Doherty Institute, The University of Melbourne, Melbourne, VIC 3000, Australia
Issue Date: 31-May-2021
metadata.dc.date: 2021-05-31
Publication information: Cancers 2021; 13(11): 2734
Abstract: (1) Background: Recent clinical and experimental data suggests that the liver's regenerative response following partial hepatectomy can stimulate tumor recurrence in the liver remnant. The Wnt/β-catenin pathway plays important roles in both colorectal cancer carcinogenesis and liver regeneration. Studies have shown that the Wnt/β-catenin pathway regulates multiple renin-angiotensin system (RAS) genes, whilst RAS inhibition (RASi) reduces tumor burden and progression. This study explores whether RASi attenuates features of tumor progression in the regenerating liver post-hepatectomy by modulating Wnt/β-catenin signaling. (2) Methods: Male CBA mice underwent CRLM induction, followed one week later by 70% partial hepatectomy. Mice were treated daily with captopril, a RASi, at 250 mg/kg/day or vehicle control from experimental Day 4. Tumor and liver samples were analyzed for RAS and Wnt signaling markers using qRT-PCR and immunohistochemistry. (3) Results: Treatment with captopril reduced the expression of down-stream Wnt target genes, including a significant reduction in both c-myc and cyclin-D1, despite activating Wnt signaling. This was a tumor-specific response that was not elicited in corresponding liver samples. (4) Conclusions: We report for the first time decreased c-myc expression in colorectal tumors following RASi treatment in vivo. Decreased c-myc expression was accompanied by an attenuated invasive phenotype, despite increased Wnt signaling.
URI: https://ahro.austin.org.au/austinjspui/handle/1/26677
DOI: 10.3390/cancers13112734
ORCID: 0000-0003-0687-5177
0000-0002-8607-4849
0000-0002-0165-1564
Journal: Cancers
PubMed URL: 34073112
ISSN: 2072-6694
Type: Journal Article
Subjects: Wnt pathway
c-myc
colorectal liver metastasis
liver regeneration
renin-angiotensin system
Appears in Collections:Journal articles

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