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Journal of Gastrointestinal Cancer
Erschienen in:

27.01.2022 | Original Research

Angiotensin II Receptor Antagonist, Valsartan, Has Beneficial Effect in Lung Metastasis of Colorectal Cancer Treated with Fluorouracil

verfasst von: Fereshteh Asgharzadeh, Niloufar Naghibzadeh, Milad Hashemzehi, Asma Mostafapour, Seyed Mahdi Hassanian, Amir Avan, Majid Khazaei

Erschienen in: Journal of Gastrointestinal Cancer | Ausgabe 1/2023

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Abstract

Purpose

Lung metastasis is the main cause of death in patients with colorectal carcinoma (CRC). Angiotensin II has been confirmed to facilitate cancer cell progression and metastasis. In this study, the possible anti-metastatic effects of an angiotensin II receptor type 1 (AT1R) antagonist, valsartan, have been investigated in an experimental CRC lung metastasis model.

Methods

An animal CRC lung metastasis model was used, involving intravenous injection of CRC cells. The experimental groups included (1) control group; (2) 5-FU (5-fluorouracil) group (5 mg/kg/every other day; ip); (3) valsartan group (40 mg/kg/day; po); and (4) valsartan + 5-FU group (combination group; valsartan 40 mg/kg/day, oral gavage, and 5-FU 5 mg/kg/every other day; ip). After 11 days, macroscopic and histological evaluations of lung tissues have been done for evaluation of lung metastatic nodules. In addition, inflammatory and angiogenic markers and oxidative stress index were measured in lung tissue.

Results

Our results showed that administration of valsartan especially in combination with 5-FU significantly reduced lung metastatic nodule and metastatic area (p < 0.05) in macroscopic and histological evaluations stained by hematoxylin–eosin. Measurement of inflammatory, angiogenic, and oxidative/antioxidative markers in lung tissue indicated that the level of IL-6, angiogenic markers (VEGF and VEGFR-1), and antioxidative markers significantly reduced in combination group (p < 0.05) while the MDA as a marker of oxidative stress increased (p < 0.05).

Conclusion

These results suggest that valsartan in combination with standard chemotherapeutic agents can have a synergistic effect in treatment of lung metastasis of CRC.
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Metadaten
Titel
Angiotensin II Receptor Antagonist, Valsartan, Has Beneficial Effect in Lung Metastasis of Colorectal Cancer Treated with Fluorouracil
verfasst von
Fereshteh Asgharzadeh
Niloufar Naghibzadeh
Milad Hashemzehi
Asma Mostafapour
Seyed Mahdi Hassanian
Amir Avan
Majid Khazaei
Publikationsdatum
27.01.2022
Verlag
Springer US
Erschienen in
Journal of Gastrointestinal Cancer / Ausgabe 1/2023
Print ISSN: 1941-6628
Elektronische ISSN: 1941-6636
DOI
https://doi.org/10.1007/s12029-021-00717-8

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