Exendin-4 Exhibits Enhanced Anti-tumor Effects in Diabetic Mice
| Autor: | Priscilla T. Y. Law, Chun-Kwok Wong, Paul K.S. Chan, Juliana C.N. Chan, Lan He |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Regulatory T cell Science Intracellular Space Antineoplastic Agents CD8-Positive T-Lymphocytes Article Proinflammatory cytokine Diabetes Mellitus Experimental 03 medical and health sciences Mice Immune system Interferon T-Lymphocyte Subsets Internal medicine Neoplasms medicine Cytotoxic T cell Animals Receptor Cells Cultured Multidisciplinary business.industry FOXP3 Disease Models Animal 030104 developmental biology medicine.anatomical_structure Endocrinology Cell Transformation Neoplastic Hyperglycemia Cytokines Exenatide Medicine business CD8 Spleen medicine.drug |
| Zdroj: | Scientific Reports, Vol 7, Iss 1, Pp 1-10 (2017) Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-017-01952-5 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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