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Blockade of the renin-angiotensin system inhibits growth of colorectal cancer liver metastases in the regenerating liver.
- Source :
-
Clinical & experimental metastasis [Clin Exp Metastasis] 2014 Apr; Vol. 31 (4), pp. 395-405. Date of Electronic Publication: 2014 Jan 18. - Publication Year :
- 2014
-
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.
- Subjects :
- Angiotensin-Converting Enzyme Inhibitors pharmacology
Animals
Apoptosis drug effects
Cell Proliferation drug effects
Colorectal Neoplasms metabolism
Colorectal Neoplasms pathology
Immunoenzyme Techniques
Liver Neoplasms metabolism
Liver Neoplasms secondary
Male
Mice
Mice, Inbred CBA
Neovascularization, Pathologic prevention & control
RNA, Messenger genetics
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Tumor Burden
Tumor Cells, Cultured
Captopril pharmacology
Colorectal Neoplasms prevention & control
Liver Neoplasms prevention & control
Liver Regeneration drug effects
Renin-Angiotensin System drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1573-7276
- Volume :
- 31
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Clinical & experimental metastasis
- Publication Type :
- Academic Journal
- Accession number :
- 24442969
- Full Text :
- https://doi.org/10.1007/s10585-014-9635-8