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Comparison of responsiveness to cancer development and anti-cancer drug in three different C57BL/6N stocks

In our efforts to understand the systemic features of tumors, the importance of animal models is increasing due to the recent growth in the development of immunotherapy and targeted therapies. This has resulted in increased attention towards tumor animal models using C57BL/6N, which are mainly used...

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Autores principales: Kang, Mi Ju, Kim, Ji Eun, Park, Ji Won, Choi, Hyeon Jun, Bae, Su Ji, Kim, Kil Soo, Jung, Young-Suk, Cho, Joon-Yong, Hwang, Dae Youn, Song, Hyun Keun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081605/
https://www.ncbi.nlm.nih.gov/pubmed/32257905
http://dx.doi.org/10.1186/s42826-019-0015-z
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author Kang, Mi Ju
Kim, Ji Eun
Park, Ji Won
Choi, Hyeon Jun
Bae, Su Ji
Kim, Kil Soo
Jung, Young-Suk
Cho, Joon-Yong
Hwang, Dae Youn
Song, Hyun Keun
author_facet Kang, Mi Ju
Kim, Ji Eun
Park, Ji Won
Choi, Hyeon Jun
Bae, Su Ji
Kim, Kil Soo
Jung, Young-Suk
Cho, Joon-Yong
Hwang, Dae Youn
Song, Hyun Keun
author_sort Kang, Mi Ju
collection PubMed
description In our efforts to understand the systemic features of tumors, the importance of animal models is increasing due to the recent growth in the development of immunotherapy and targeted therapies. This has resulted in increased attention towards tumor animal models using C57BL/6N, which are mainly used in immunological studies. In this study, the C57BL/6NKorl stock and two other commercial stocks (C57BL/6NA and C57BL/N6B) are evaluated by comparing the occurrence of tumors using the syngeneic model; furthermore, we compare the response to anti-cancer drugs in the syngeneic model by evaluating survival, growth of tumors, proliferation and molecular biology analysis. In the syngeneic model using LLC (Lewis lung carcinoma) cells, the survival of mice and growth of the tumor showed a better response in the C57BL/6NKorl stock, and was dependent on the cell concentration of the dosing tumor, as compared to the other C57BL/6N stocks. However, the Ki-67 staining showed only little difference in cell proliferation within the tumor tissue each mouse stocks. Comparing the sensitivity to anti-cancer drug by examining changes in growth, volume and weight revealed that cisplatin treatment for tumor-bearing C57BL/6NKorl was more dependent on concentration. The Ki-67 staining, however, showed no difference among the C57BL/6N stocks after cisplatin treatment. The expressions of p27 and p53 tumor suppressor proteins, caspase-3 and Bax showed dose-dependent increase after exposure to cisplatin, whereas the expression of Bcl-2 was reduced in a dose-dependent manner. Furthermore, the expressions of MMP-2 and VEGF involved in metastasis, as well as inflammatory genes IL-1β, IL-6 and IL-10, showed dose-dependent decrease in tumor tissue after cisplatin exposure. Differences observed among the C57BL/6N stocks were not significant. Taken together, our studies reveal that C57BL/6NKorl has the potential of being a useful biological resource established in Korea, as it does not differ from the two commercially available C57BL/6N stocks when considering response to tumor generation and sensitivity to anti-cancer drugs using the syngeneic tumor model. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s42826-019-0015-z) contains supplementary material, which is available to authorized users.
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spelling pubmed-70816052020-04-01 Comparison of responsiveness to cancer development and anti-cancer drug in three different C57BL/6N stocks Kang, Mi Ju Kim, Ji Eun Park, Ji Won Choi, Hyeon Jun Bae, Su Ji Kim, Kil Soo Jung, Young-Suk Cho, Joon-Yong Hwang, Dae Youn Song, Hyun Keun Lab Anim Res Research In our efforts to understand the systemic features of tumors, the importance of animal models is increasing due to the recent growth in the development of immunotherapy and targeted therapies. This has resulted in increased attention towards tumor animal models using C57BL/6N, which are mainly used in immunological studies. In this study, the C57BL/6NKorl stock and two other commercial stocks (C57BL/6NA and C57BL/N6B) are evaluated by comparing the occurrence of tumors using the syngeneic model; furthermore, we compare the response to anti-cancer drugs in the syngeneic model by evaluating survival, growth of tumors, proliferation and molecular biology analysis. In the syngeneic model using LLC (Lewis lung carcinoma) cells, the survival of mice and growth of the tumor showed a better response in the C57BL/6NKorl stock, and was dependent on the cell concentration of the dosing tumor, as compared to the other C57BL/6N stocks. However, the Ki-67 staining showed only little difference in cell proliferation within the tumor tissue each mouse stocks. Comparing the sensitivity to anti-cancer drug by examining changes in growth, volume and weight revealed that cisplatin treatment for tumor-bearing C57BL/6NKorl was more dependent on concentration. The Ki-67 staining, however, showed no difference among the C57BL/6N stocks after cisplatin treatment. The expressions of p27 and p53 tumor suppressor proteins, caspase-3 and Bax showed dose-dependent increase after exposure to cisplatin, whereas the expression of Bcl-2 was reduced in a dose-dependent manner. Furthermore, the expressions of MMP-2 and VEGF involved in metastasis, as well as inflammatory genes IL-1β, IL-6 and IL-10, showed dose-dependent decrease in tumor tissue after cisplatin exposure. Differences observed among the C57BL/6N stocks were not significant. Taken together, our studies reveal that C57BL/6NKorl has the potential of being a useful biological resource established in Korea, as it does not differ from the two commercially available C57BL/6N stocks when considering response to tumor generation and sensitivity to anti-cancer drugs using the syngeneic tumor model. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s42826-019-0015-z) contains supplementary material, which is available to authorized users. BioMed Central 2019-10-04 /pmc/articles/PMC7081605/ /pubmed/32257905 http://dx.doi.org/10.1186/s42826-019-0015-z Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Kang, Mi Ju
Kim, Ji Eun
Park, Ji Won
Choi, Hyeon Jun
Bae, Su Ji
Kim, Kil Soo
Jung, Young-Suk
Cho, Joon-Yong
Hwang, Dae Youn
Song, Hyun Keun
Comparison of responsiveness to cancer development and anti-cancer drug in three different C57BL/6N stocks
title Comparison of responsiveness to cancer development and anti-cancer drug in three different C57BL/6N stocks
title_full Comparison of responsiveness to cancer development and anti-cancer drug in three different C57BL/6N stocks
title_fullStr Comparison of responsiveness to cancer development and anti-cancer drug in three different C57BL/6N stocks
title_full_unstemmed Comparison of responsiveness to cancer development and anti-cancer drug in three different C57BL/6N stocks
title_short Comparison of responsiveness to cancer development and anti-cancer drug in three different C57BL/6N stocks
title_sort comparison of responsiveness to cancer development and anti-cancer drug in three different c57bl/6n stocks
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081605/
https://www.ncbi.nlm.nih.gov/pubmed/32257905
http://dx.doi.org/10.1186/s42826-019-0015-z
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