氯沙坦
医学
氧化应激
转移
丙二醛
肺癌
结直肠癌
血管生成
超氧化物歧化酶
血管紧张素II
癌症研究
血管内皮生长因子
内科学
药理学
癌症
受体
血管内皮生长因子受体
作者
Milad Hashemzehi,Niloufar Naghibzadeh,Fereshteh Asgharzadeh,Asma Mostafapour,Seyed Mahdi Hassanian,Gordon A. Ferns,William C. Cho,Amir Avan,Majid Khazaei
出处
期刊:PubMed
日期:2020-01-01
卷期号:19: 927-935
被引量:11
标识
DOI:10.17179/excli2020-2093
摘要
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.
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