The therapeutic potential of losartan in lung metastasis of colorectal cancer

Authors

  • Milad Hashemzehi Department of Medical Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
  • Niloufar Naghibzadeh Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
  • Fereshteh Asgharzadeh Department of Medical Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
  • Asma Mostafapour Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
  • Seyed Mahdi Hassanian Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
  • Gordon A. Ferns Brighton & Sussex Medical School, Division of Medical Education, Falmer, Brighton, Sussex BN1 9PH, UK
  • William C. Cho Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong, China
  • Amir Avan Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Tel: +98 513 8002298; E-mail: avana@mums.ac.ir
  • Majid Khazaei Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Tel: +98 513 8002298; E-mail: Khazaeim@mums.ac.ir

DOI:

https://doi.org/10.17179/excli2020-2093

Keywords:

renin-angiotensin system, losartan, colorectal cancercolorectal cancer, lung metastasis

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.

Published

2020-06-29

How to Cite

Hashemzehi, M., Naghibzadeh, N., Asgharzadeh, F., Mostafapour, A., Hassanian, S. M., Ferns, G. 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

Issue

Section

Original articles

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