Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/12052
Title: Blockade of the renin-angiotensin system inhibits growth of colorectal cancer liver metastases in the regenerating liver
Authors: Koh, Shir Lin;Ager, E I;Costa, P L N;Malcontenti-Wilson, Caterina;Muralidharan, Vigayaragavan;Christophi, Christopher
Affiliation: Department of Surgery, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Issue Date: 18-Jan-2014
Citation: Clinical & Experimental Metastasis 2014; 31(4): 395-405
Abstract: Partial hepatectomy (PH), the preferred option for selected patients with colorectal cancer liver metastases (CRCLM), is associated with 40-80 % tumor recurrence rates. Renin-angiotensin system (RAS) blockade inhibits tumor growth and has been suggested to improve liver regeneration. We documented the effect of RAS blockade on tumor growth and liver regeneration in a murine model. CRCLM induction followed by 70 % PH was performed on 78 CBA mice. Liver regeneration (days 2, 6) and CRCLM tumor load were measured by liver (and tumor) weights, percentage of CRCLM burden and tumor nodule count (days 16, 21). mRNA expression of the RAS components was characterised. Statistical analysis was performed using 2-independent sample T test or Mann-Whitney test (SPSS). Captopril did not impair liver regeneration. By day 21, Captopril decreased tumor burden (percentage of CRCLM in the liver) (48.7 ± 4.7 % control, 24.4 ± 6.2 Captopril; p = 0.008), tumor volume (1046.2 ± 200.2 mm(3), 388.3 ± 150.4; p = 0.02), tumor nodule count per image field (181.1 ± 28.5, 68 ± 17.6; p = 0.005) and tumor angiogenesis (71.8 ± 6.4 vessels/mm(2), 43.1 ± 7.6; p = 0.015) compared to controls. Captopril enhanced tumor apoptosis (1 ± 0.2 %, 2.5 ± 0.7; p = 0.028). Liver regeneration and tumor development increased liver ACE levels. Blockade of the RAS effectively retarded CRCLM tumor growth at the late stage of tumor development within the regenerating liver without impeding liver regeneration following PH, via anti-angiogenesis and pro-tumor apoptosis. Captopril may be of therapeutic benefit in patients undergoing PH for CRCLM.
Internal ID Number: 24442969
URI: http://ahro.austin.org.au/austinjspui/handle/1/12052
DOI: 10.1007/s10585-014-9635-8
URL: http://www.ncbi.nlm.nih.gov/pubmed/24442969
Type: Journal Article
Appears in Collections:Journal articles

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