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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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The Korean Society for Radiation Oncology
2016
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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. |
format | Online Article Text |
id | pubmed-5066444 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The Korean Society for Radiation Oncology |
record_format | MEDLINE/PubMed |
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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