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Sirolimus and Metformin Synergistically Inhibits Colon Cancer In Vitro and In Vivo

We estimated the effect of various immunosuppressants (ISs) and metformin (M) to provide theoretical background of optimal therapeutic strategy for de novo colon cancer after liver transplantation (LT). Three colon cancer cell lines (HT29, SW620, and HCT116) were used in in vitro studies. HT29 was a...

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Autores principales: Mussin, Nadiar, Oh, Seung Cheol, Lee, Kwang-Woong, Park, Min Young, Seo, Sooin, Yi, Nam-Joon, Kim, Hyeyoung, Yoon, Kyung Chul, Ahn, Sung-Woo, Kim, Hyo-Sin, Hong, Suk Kyun, Oh, Dong Kyu, Suh, Kyung-Suk
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Academy of Medical Sciences 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5546956/
https://www.ncbi.nlm.nih.gov/pubmed/28776332
http://dx.doi.org/10.3346/jkms.2017.32.9.1385
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author Mussin, Nadiar
Oh, Seung Cheol
Lee, Kwang-Woong
Park, Min Young
Seo, Sooin
Yi, Nam-Joon
Kim, Hyeyoung
Yoon, Kyung Chul
Ahn, Sung-Woo
Kim, Hyo-Sin
Hong, Suk Kyun
Oh, Dong Kyu
Suh, Kyung-Suk
author_facet Mussin, Nadiar
Oh, Seung Cheol
Lee, Kwang-Woong
Park, Min Young
Seo, Sooin
Yi, Nam-Joon
Kim, Hyeyoung
Yoon, Kyung Chul
Ahn, Sung-Woo
Kim, Hyo-Sin
Hong, Suk Kyun
Oh, Dong Kyu
Suh, Kyung-Suk
author_sort Mussin, Nadiar
collection PubMed
description We estimated the effect of various immunosuppressants (ISs) and metformin (M) to provide theoretical background of optimal therapeutic strategy for de novo colon cancer after liver transplantation (LT). Three colon cancer cell lines (HT29, SW620, and HCT116) were used in in vitro studies. HT29 was also used in BALB/c-nude mice animal models. Following groups were used in both in vitro and in vivo studies: sirolimus (S), tacrolimus (T), cyclosporin A (CsA), M, metformin/sirolimus (Met/S), metformin/tacrolimus (Met/T), and metformin/cyclosporin A (Met/CsA). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed and western blot analyses were performed for mTOR pathway proteins, apoptosis proteins, and epithelial-mesenchymal-transition (EMT) proteins. Tumor volume was measured for 4 weeks after inoculation. MTT-assay revealed significant cell viability inhibition in all 3 colon cancer cell lines in groups of S, M, and Met/S. Of note, group Met/S showed synergistic effect compare to M or S group. Western blot analysis showed significant low levels of all investigated proteins in groups of S and Met/S in both in vitro and in vivo experiment. Tumor growth was significantly inhibited only in the Met/S group. Combination of Met and S showed the most potent inhibition in all colon cancer cell lines. This finding might have application for de novo colon cancer.
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spelling pubmed-55469562017-09-01 Sirolimus and Metformin Synergistically Inhibits Colon Cancer In Vitro and In Vivo Mussin, Nadiar Oh, Seung Cheol Lee, Kwang-Woong Park, Min Young Seo, Sooin Yi, Nam-Joon Kim, Hyeyoung Yoon, Kyung Chul Ahn, Sung-Woo Kim, Hyo-Sin Hong, Suk Kyun Oh, Dong Kyu Suh, Kyung-Suk J Korean Med Sci Original Article We estimated the effect of various immunosuppressants (ISs) and metformin (M) to provide theoretical background of optimal therapeutic strategy for de novo colon cancer after liver transplantation (LT). Three colon cancer cell lines (HT29, SW620, and HCT116) were used in in vitro studies. HT29 was also used in BALB/c-nude mice animal models. Following groups were used in both in vitro and in vivo studies: sirolimus (S), tacrolimus (T), cyclosporin A (CsA), M, metformin/sirolimus (Met/S), metformin/tacrolimus (Met/T), and metformin/cyclosporin A (Met/CsA). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed and western blot analyses were performed for mTOR pathway proteins, apoptosis proteins, and epithelial-mesenchymal-transition (EMT) proteins. Tumor volume was measured for 4 weeks after inoculation. MTT-assay revealed significant cell viability inhibition in all 3 colon cancer cell lines in groups of S, M, and Met/S. Of note, group Met/S showed synergistic effect compare to M or S group. Western blot analysis showed significant low levels of all investigated proteins in groups of S and Met/S in both in vitro and in vivo experiment. Tumor growth was significantly inhibited only in the Met/S group. Combination of Met and S showed the most potent inhibition in all colon cancer cell lines. This finding might have application for de novo colon cancer. The Korean Academy of Medical Sciences 2017-09 2017-07-28 /pmc/articles/PMC5546956/ /pubmed/28776332 http://dx.doi.org/10.3346/jkms.2017.32.9.1385 Text en © 2017 The Korean Academy of Medical Sciences. https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://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
Mussin, Nadiar
Oh, Seung Cheol
Lee, Kwang-Woong
Park, Min Young
Seo, Sooin
Yi, Nam-Joon
Kim, Hyeyoung
Yoon, Kyung Chul
Ahn, Sung-Woo
Kim, Hyo-Sin
Hong, Suk Kyun
Oh, Dong Kyu
Suh, Kyung-Suk
Sirolimus and Metformin Synergistically Inhibits Colon Cancer In Vitro and In Vivo
title Sirolimus and Metformin Synergistically Inhibits Colon Cancer In Vitro and In Vivo
title_full Sirolimus and Metformin Synergistically Inhibits Colon Cancer In Vitro and In Vivo
title_fullStr Sirolimus and Metformin Synergistically Inhibits Colon Cancer In Vitro and In Vivo
title_full_unstemmed Sirolimus and Metformin Synergistically Inhibits Colon Cancer In Vitro and In Vivo
title_short Sirolimus and Metformin Synergistically Inhibits Colon Cancer In Vitro and In Vivo
title_sort sirolimus and metformin synergistically inhibits colon cancer in vitro and in vivo
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5546956/
https://www.ncbi.nlm.nih.gov/pubmed/28776332
http://dx.doi.org/10.3346/jkms.2017.32.9.1385
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