The therapeutic potential of losartan in lung metastasis of colorectal cancer

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dc.contributor.authorHashemzehi, Milad
dc.contributor.authorNaghibzadeh, Niloufar
dc.contributor.authorAsgharzadeh, Fereshteh
dc.contributor.authorMostafapour, Asma
dc.contributor.authorHassanian, Seyed Mahdi
dc.contributor.authorFerns, Gordon A.
dc.contributor.authorCho, William C.
dc.contributor.authorAvan, Amir
dc.contributor.authorKhazaei, Majid
dc.date.accessioned2020-12-11T13:42:37Z
dc.date.available2020-12-11T13:42:37Z
dc.date.issued2020-06-29
dc.description.abstractColorectal 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.en
dc.identifier.citationHashemzehi, 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/excli2020-2093en
dc.identifier.issn1611-2156
dc.identifier.urihttp://hdl.handle.net/2003/39878
dc.identifier.urihttp://dx.doi.org/10.17877/DE290R-21769
dc.language.isoen
dc.publisherIfADo - Leibniz Research Centre for Working Environment and Human Factors, Dortmunden
dc.relation.ispartofseriesEXCLI Journal;Vol. 19 2020
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectRenin-angiotensin systemen
dc.subjectLosartanen
dc.subjectColorectal canceren
dc.subjectLung metastasisen
dc.subject.ddc610
dc.titleThe therapeutic potential of losartan in lung metastasis of colorectal canceren
dc.typeText
dc.type.publicationtypearticle
dcterms.accessRightsopen access
eldorado.dnb.zdberstkatid2132560-1
eldorado.identifier.urlhttps://www.excli.de/index.php/excli/article/view/2093
eldorado.secondarypublicationtrue

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