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

Scientific Reports
Lan HePaul K S Chan

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 immunomodula...Continue Reading

References

Sep 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·B Thorens
May 25, 2006·Neuroscience Research·Takashi IwaiJun-Ichiro Oka
Aug 4, 2006·Cancer Research·Ido WolfH Phillip Koeffler
Aug 22, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Gaby PalmerCem Gabay
Oct 24, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Laurence MaciaIsabelle Wolowczuk
Jun 20, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Qiang GaoZhao-You Tang
Dec 17, 2009·International Journal of Cancer. Journal International Du Cancer·Chien-Hung LeeMing-Tsang Wu
Sep 21, 2010·International Journal of STD & AIDS·M YongC O'Mahony
Feb 10, 2012·Diabetes/metabolism Research and Reviews·Xilin YangJuliana C N Chan
Sep 3, 2013·The New England Journal of Medicine·Benjamin M SciricaUNKNOWN SAVOR-TIMI 53 Steering Committee and Investigators
May 8, 2014·American Journal of Physiology. Endocrinology and Metabolism·Hejun ZhaoTianpei Hong
Jun 1, 2014·Diabetes·Takashi NomiyamaToshihiko Yanase
Jan 28, 2015·Proceedings of the National Academy of Sciences of the United States of America·Shingo EikawaHeiichiro Udono
Mar 25, 2015·Nature Reviews. Endocrinology·Xilin YangJuliana C N Chan
Jun 9, 2015·The New England Journal of Medicine·Jennifer B GreenUNKNOWN TECOS Study Group

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Citations

Aug 17, 2018·Bioscience Reports·Peter ShyuGuillaume Thibault
Aug 31, 2018·Brain : a Journal of Neurology·Eridan Rocha-FerreiraAhad A Rahim

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Methods Mentioned

BETA
xenograft
flow cytometry
ELISA
Assay

Software Mentioned

CELLQuest

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