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Immunomodulatory effect of captopril and local irradiation on myeloid-derived suppressor cells

PURPOSE: This study is to investigate the effect of captopril when combined with irradiation. MATERIALS AND METHODS: 4T1 (mouse mammary carcinoma) cells were injected in the right hind leg of Balb/c mice. Mice were randomized to four groups; control (group 1), captopril-treated (group 2), irradiated...

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Autores principales: Cho, Won Kyung, Shin, Sung-Won, Kim, Shin-Yeong, Hong, Chang-Won, Choi, Changhoon, Park, Won, Noh, Jae Myoung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Society for Radiation Oncology 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5066444/
https://www.ncbi.nlm.nih.gov/pubmed/27609109
http://dx.doi.org/10.3857/roj.2016.01816
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author Cho, Won Kyung
Shin, Sung-Won
Kim, Shin-Yeong
Hong, Chang-Won
Choi, Changhoon
Park, Won
Noh, Jae Myoung
author_facet Cho, Won Kyung
Shin, Sung-Won
Kim, Shin-Yeong
Hong, Chang-Won
Choi, Changhoon
Park, Won
Noh, Jae Myoung
author_sort Cho, Won Kyung
collection PubMed
description PURPOSE: This study is to investigate the effect of captopril when combined with irradiation. MATERIALS AND METHODS: 4T1 (mouse mammary carcinoma) cells were injected in the right hind leg of Balb/c mice. Mice were randomized to four groups; control (group 1), captopril-treated (group 2), irradiated (group 3), irradiated and captopril-treated concurrently (group 4). Captopril was administered by intraperitoneal injection (10 mg/kg) daily and irradiation was delivered on the tumor-bearing leg for 15 Gy in 3 fractions. Surface markers of splenic neutrophils (G-MDSCs) and intratumoral neutrophils (tumor-associated neutrophils [TANs]) were assessed using flow cytometry and expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 alpha (HIF-1α) of tumor was evaluated by immunohistochemical (IHC) staining. RESULTS: The mean tumor volumes (±standard error) at the 15th day after randomization were 1,382.0 (±201.2) mm(3) (group 1), 559.9 (±67.8) mm(3) (group 3), and 370.5 (± 48.1) mm(3) (group 4), respectively. For G-MDSCs, irradiation reversed decreased expression of CD101 from tumor-bearing mice, and additional increase of CD101 expression was induced by captopril administration. Similar tendency was observed in TANs. The expression of tumor-necrosis factor-associated molecules, CD120 and CD137, are increased by irradiation in both G-MDSCs and TANs. Further increment was observed by captopril except CD120 in TANs. For IHC staining, VEGF and HIF-1α positivity in tumor cells were decreased when treated with captopril. CONCLUSION: Captopril is suggested to have additional effect when combined to irradiation in a murine tumor model by modulation of MDSCs and angiogenesis.
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spelling pubmed-50664442016-10-18 Immunomodulatory effect of captopril and local irradiation on myeloid-derived suppressor cells Cho, Won Kyung Shin, Sung-Won Kim, Shin-Yeong Hong, Chang-Won Choi, Changhoon Park, Won Noh, Jae Myoung Radiat Oncol J Original Article PURPOSE: This study is to investigate the effect of captopril when combined with irradiation. MATERIALS AND METHODS: 4T1 (mouse mammary carcinoma) cells were injected in the right hind leg of Balb/c mice. Mice were randomized to four groups; control (group 1), captopril-treated (group 2), irradiated (group 3), irradiated and captopril-treated concurrently (group 4). Captopril was administered by intraperitoneal injection (10 mg/kg) daily and irradiation was delivered on the tumor-bearing leg for 15 Gy in 3 fractions. Surface markers of splenic neutrophils (G-MDSCs) and intratumoral neutrophils (tumor-associated neutrophils [TANs]) were assessed using flow cytometry and expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 alpha (HIF-1α) of tumor was evaluated by immunohistochemical (IHC) staining. RESULTS: The mean tumor volumes (±standard error) at the 15th day after randomization were 1,382.0 (±201.2) mm(3) (group 1), 559.9 (±67.8) mm(3) (group 3), and 370.5 (± 48.1) mm(3) (group 4), respectively. For G-MDSCs, irradiation reversed decreased expression of CD101 from tumor-bearing mice, and additional increase of CD101 expression was induced by captopril administration. Similar tendency was observed in TANs. The expression of tumor-necrosis factor-associated molecules, CD120 and CD137, are increased by irradiation in both G-MDSCs and TANs. Further increment was observed by captopril except CD120 in TANs. For IHC staining, VEGF and HIF-1α positivity in tumor cells were decreased when treated with captopril. CONCLUSION: Captopril is suggested to have additional effect when combined to irradiation in a murine tumor model by modulation of MDSCs and angiogenesis. The Korean Society for Radiation Oncology 2016-09 2016-09-13 /pmc/articles/PMC5066444/ /pubmed/27609109 http://dx.doi.org/10.3857/roj.2016.01816 Text en Copyright © 2016 The Korean Society for Radiation Oncology This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/ (http://creativecommons.org/licenses/by-nc/4.0) ) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Cho, Won Kyung
Shin, Sung-Won
Kim, Shin-Yeong
Hong, Chang-Won
Choi, Changhoon
Park, Won
Noh, Jae Myoung
Immunomodulatory effect of captopril and local irradiation on myeloid-derived suppressor cells
title Immunomodulatory effect of captopril and local irradiation on myeloid-derived suppressor cells
title_full Immunomodulatory effect of captopril and local irradiation on myeloid-derived suppressor cells
title_fullStr Immunomodulatory effect of captopril and local irradiation on myeloid-derived suppressor cells
title_full_unstemmed Immunomodulatory effect of captopril and local irradiation on myeloid-derived suppressor cells
title_short Immunomodulatory effect of captopril and local irradiation on myeloid-derived suppressor cells
title_sort immunomodulatory effect of captopril and local irradiation on myeloid-derived suppressor cells
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5066444/
https://www.ncbi.nlm.nih.gov/pubmed/27609109
http://dx.doi.org/10.3857/roj.2016.01816
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