The therapeutic potential of losartan in lung metastasis of colorectal cancer
Loading...
Date
2020-06-29
Journal Title
Journal ISSN
Volume Title
Publisher
IfADo - Leibniz Research Centre for Working Environment and Human Factors, Dortmund
Alternative Title(s)
Abstract
Colorectal cancer (CRC) is a common cancer with a high incidence rate. Components of the renin-angiotensin system (RAS) have been reported to be dysregulated in several malignancies including CRC. Here, we have explored the potential anti-metastatic effects of a RAS inhibitor, losartan, in an experimental model of lung metastasis in CRC. A murine model of lung metastasis of CRC was used, which involved the intravenous injection of CT26 cells via a tail vein. Four experimental groups comprised: an untreated group; a group that received 5-FU which was administered intraperitoneally; a losartan group that received a combination group that received 5-FU plus losartan . We evaluated the anti-inflammatory effects of losartan by histopathological method, and the measurement of oxidative or antioxidant markers including malondialdehyde (MDA) and total-thiols (T-SH) tissue levels, superoxide-dismutase (SOD) and catalase activity. We found that losartan inhibited lung metastasis of CRC and there was a reduction of the IL-6 expression level in the tissue sample. It was also associated with reduced levels of the anti-angiogenic factor Vascular endothelial growth factor (VEGF). Furthermore, we found that losartan induced oxidative stress as assessed by an elevation of MDA level, reduction of T-SH, SOD and catalase activities in lung tissue. Our findings demonstrated that losartan ameliorates angiogenesis, inflammation and the induction of oxidative stress via Angiotensin II type I receptor (AT1R). This may shine some lights on targeting the RAS pathway as a potential therapeutic approach in the treatment of metastatic CRC patients.
Description
Table of contents
Keywords
Renin-angiotensin system, Losartan, Colorectal cancer, Lung metastasis
Subjects based on RSWK
Citation
Hashemzehi, M., Naghibzadeh, N., Asgharzadeh, F., Mostafapour, A., Hassanian, S. M., Ferns, G. A., Cho, W. C., Avan, A., & Khazaei, M. (2020). The therapeutic potential of losartan in lung metastasis of colorectal cancer. EXCLI Journal, 19, 927-935. https://doi.org/10.17179/excli2020-2093