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Title
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Suppression of lung metastases by the CD26/DPP4 inhibitor Vildagliptin in mice
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Author
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Abstract
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| Metastases rather than primary cancers determine nowadays the survival of patients. One of the most common primary malignancies is colorectal cancer and this type of tumor is characterized by a high tendency to spread metastases to the lung and liver. CD26/DPP4 is a transmembrane molecule with enzymatic functions which cleaves biologically active peptides. Recently, CD26/DPP4 has become the focus of cancer research and it was shown that CD26/DPP4-positive cancer cells display increased metastatic activity. Here, we tested if the CD26/DPP4-inhibitor Vildagliptin suppresses the development and growth of mouse colorectal lung metastases. This inhibitor of CD26/DPP4 was employed on mouse (C57BL/6) colorectal lung metastases, established by intravenous injection of the syngeneic cell line MC38. For mechanistic analysis, a subcutaneous tumor model was used. The treatment with Vildagliptin significantly suppressed both, the incidence and growth of lung metastases. Autophagy markers (LC3, p62, and ATF4) decreased, apoptosis increased (TUNEL, pH3/Ki-76), and the cell cycle regulator pCDC2 was inhibited. In conclusion, we here showed an anti-tumor effect of Vildagliptin via downregulation of autophagy resulting in increased apoptosis and modulation of the cell cycle. We therefore propose Vildagliptin for the evaluation as a new therapeutic approach for the treatment of colorectal cancer lung metastases. |
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Language
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English
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Source (journal)
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Clinical and experimental metastasis. - Basingstoke
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Publication
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Basingstoke
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2015
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ISSN
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0262-0898
[print]
1573-7276
[online]
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DOI
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10.1007/S10585-015-9736-Z
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Volume/pages
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32
:7
(2015)
, p. 677-687
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ISI
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000361715300004
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Pubmed ID
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26233333
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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