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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.

SUBMITTER: Hashemzehi M

PROVIDER: S-EPMC7355150 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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The therapeutic potential of losartan in lung metastasis of colorectal cancer.

Hashemzehi Milad M Naghibzadeh Niloufar N Asgharzadeh Fereshteh F Mostafapour Asma A Hassanian Seyed Mahdi SM Ferns Gordon A GA Cho William C WC Avan Amir A Khazaei Majid M

EXCLI journal 20200629

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: a ...[more]

PMID: 32665776

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The therapeutic potential of losartan in lung metastasis of colorectal cancer.

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The therapeutic potential of losartan in lung metastasis of colorectal cancer.

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