Hassanian, Seyed Mahdi
Ferns, Gordon A.
Cho, William C.
|Title:||The therapeutic potential of losartan in lung metastasis of colorectal cancer|
|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.|
|Subject Headings:||Renin-angiotensin system|
|Provenance:||IfADo - Leibniz Research Centre for Working Environment and Human Factors, Dortmund|
|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|
|Appears in Collections:||Original Articles 2020|
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