Exendin-4 Exhibits Enhanced Anti-tumor Effects in Diabetic Mice

Abstract Type 2 diabetes (T2D) is associated with increased risk of cancers. In this connection, we previously demonstrated the promoting effect of diabetes on HPV-associated carcinogenesis using a xenograft model in db/db diabetic mice. The underlying mechanism of this observation might be partly c...

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Autores principales:	Lan He, Priscilla T. Y. Law, Chun Kwok Wong, Juliana C. N. Chan, Paul K. S. Chan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/215cb506569d4afd9eb21f6ffa6b63db
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spelling	oai:doaj.org-article:215cb506569d4afd9eb21f6ffa6b63db2021-12-02T12:32:29ZExendin-4 Exhibits Enhanced Anti-tumor Effects in Diabetic Mice10.1038/s41598-017-01952-52045-2322https://doaj.org/article/215cb506569d4afd9eb21f6ffa6b63db2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01952-5https://doaj.org/toc/2045-2322Abstract Type 2 diabetes (T2D) is associated with increased risk of cancers. In this connection, we previously demonstrated the promoting effect of diabetes on HPV-associated carcinogenesis using a xenograft model in db/db diabetic mice. The underlying mechanism of this observation might be partly contributed by dysregulated immune response in diabetes. In this study, we hypothesized that the impaired anti-tumor immune response in diabetic status could be modulated by exendin-4, a glucagon-like protein receptor agonist which exhibits anti-diabetic effects. We inoculated 10-week old db/db mice with 2 × 107 CUP-1 cells (Human Papilloma Virus (HPV)-16 E7 transfected continuous cell line) subcutaneously underneath the scruff, and treated mice with high (30 nmol/kg) or low (10 nmol/kg) dose of exendin-4 for 13 days. Compared with control groups, exendin-4 suppressed subcutaneous tumor growth in a dose-dependent manner, accompanied by increased interferon (IFN)-γ secreting CD8+ cytotoxic T lymphocyte (CTL)/Foxp3+ regulatory T cell (Treg) ratio as well as Th1 proinflammatory cytokines IFN-γ and IL-2. Collectively, these findings suggested an anti-tumor effect of exendin-4 in diabetic conditions, which might be resulted from direct immunomodulation.Lan HePriscilla T. Y. LawChun Kwok WongJuliana C. N. ChanPaul K. S. ChanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lan He Priscilla T. Y. Law Chun Kwok Wong Juliana C. N. Chan Paul K. S. Chan Exendin-4 Exhibits Enhanced Anti-tumor Effects in Diabetic Mice
description	Abstract Type 2 diabetes (T2D) is associated with increased risk of cancers. In this connection, we previously demonstrated the promoting effect of diabetes on HPV-associated carcinogenesis using a xenograft model in db/db diabetic mice. The underlying mechanism of this observation might be partly contributed by dysregulated immune response in diabetes. In this study, we hypothesized that the impaired anti-tumor immune response in diabetic status could be modulated by exendin-4, a glucagon-like protein receptor agonist which exhibits anti-diabetic effects. We inoculated 10-week old db/db mice with 2 × 107 CUP-1 cells (Human Papilloma Virus (HPV)-16 E7 transfected continuous cell line) subcutaneously underneath the scruff, and treated mice with high (30 nmol/kg) or low (10 nmol/kg) dose of exendin-4 for 13 days. Compared with control groups, exendin-4 suppressed subcutaneous tumor growth in a dose-dependent manner, accompanied by increased interferon (IFN)-γ secreting CD8+ cytotoxic T lymphocyte (CTL)/Foxp3+ regulatory T cell (Treg) ratio as well as Th1 proinflammatory cytokines IFN-γ and IL-2. Collectively, these findings suggested an anti-tumor effect of exendin-4 in diabetic conditions, which might be resulted from direct immunomodulation.
format	article
author	Lan He Priscilla T. Y. Law Chun Kwok Wong Juliana C. N. Chan Paul K. S. Chan
author_facet	Lan He Priscilla T. Y. Law Chun Kwok Wong Juliana C. N. Chan Paul K. S. Chan
author_sort	Lan He
title	Exendin-4 Exhibits Enhanced Anti-tumor Effects in Diabetic Mice
title_short	Exendin-4 Exhibits Enhanced Anti-tumor Effects in Diabetic Mice
title_full	Exendin-4 Exhibits Enhanced Anti-tumor Effects in Diabetic Mice
title_fullStr	Exendin-4 Exhibits Enhanced Anti-tumor Effects in Diabetic Mice
title_full_unstemmed	Exendin-4 Exhibits Enhanced Anti-tumor Effects in Diabetic Mice
title_sort	exendin-4 exhibits enhanced anti-tumor effects in diabetic mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/215cb506569d4afd9eb21f6ffa6b63db
work_keys_str_mv	AT lanhe exendin4exhibitsenhancedantitumoreffectsindiabeticmice AT priscillatylaw exendin4exhibitsenhancedantitumoreffectsindiabeticmice AT chunkwokwong exendin4exhibitsenhancedantitumoreffectsindiabeticmice AT julianacnchan exendin4exhibitsenhancedantitumoreffectsindiabeticmice AT paulkschan exendin4exhibitsenhancedantitumoreffectsindiabeticmice
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Exendin-4 Exhibits Enhanced Anti-tumor Effects in Diabetic Mice

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