Suppression of lung metastases by the CD26/DPP4 inhibitor Vildagliptin in mice
Male
0301 basic medicine
Cancer Research
Lung Neoplasms
Pyrrolidines
Dipeptidyl Peptidase 4
610 Medicine & health
Adamantane
Antineoplastic Agents
Apoptosis
142-005 142-005
7. Clean energy
Mice
03 medical and health sciences
Cell Line, Tumor
Nitriles
In Situ Nick-End Labeling
Animals
Humans
1306 Cancer Research
Vildagliptin
0303 health sciences
General Medicine
Neoplasms, Experimental
Xenograft Model Antitumor Assays
3. Good health
Mice, Inbred C57BL
Oncology
2730 Oncology
Human medicine
Colorectal Neoplasms
DOI:
10.1007/s10585-015-9736-z
Publication Date:
2015-08-01T04:21:37Z
AUTHORS (9)
ABSTRACT
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.
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (35)
CITATIONS (61)
EXTERNAL LINKS
PlumX Metrics
RECOMMENDATIONS
FAIR ASSESSMENT
Coming soon ....
JUPYTER LAB
Coming soon ....