Back to Search
Start Over
Establishment of a novel human cell line retaining the characteristics of the original pancreatic adenocarcinoma, and evaluation of MEK as a therapeutic target
- Source :
- International Journal of Oncology
- Publication Year :
- 2020
- Publisher :
- D.A. Spandidos, 2020.
-
Abstract
- Pancreatic cancer is a lethal solid malignancy with limited therapeutic options. The development of novel therapeutic drugs requires adequate new cell line models. A new pancreatic cancer cell line, designated PDXPC1, was established from one pancreatic ductal adenocarcinoma (PDAC) patient-derived xenograft. The PDXPC1 cells were stably cultured for >2 years and had a stable short tandem repeat profile. The PDXPC1 cell line retained the key mutations of the primary tumor, along with the epithelial origin and other important protein expression. The PDXPC1 cells induced rapid in vivo tumor growth, both subcutaneously and orthotopically, in a mouse model with an elevated CA199 level. The PDXPC1 cells showed weak growth, invasion and migration potency compared to another pancreatic cancer cell line, but were relatively resistant to multiple anti-cancer drugs. Interestingly, the MEK inhibitor trametinib significantly inhibited the proliferation of PDXPC1 cells, and not that of Panc-1 cells, by inactivating MEK/ERK/MYC signaling and activating the apoptotic pathway via Bcl-2 degradation. In conclusion, the PDXPC1 cell line, capturing the major characteristics of the primary tumor, may be a suitable tool for studying the underlying mechanisms of chemo-resistance in PDAC and developing new targeted therapeutic options.
- Subjects :
- 0301 basic medicine
MAPK/ERK pathway
Cancer Research
Cell Survival
Pyridones
Cell
Cell Culture Techniques
pancreatic ductal adenocarcinoma
Pyrimidinones
cell lines
Biology
Mice
03 medical and health sciences
0302 clinical medicine
Pancreatic cancer
Tumor Cells, Cultured
medicine
Animals
Humans
Protein Kinase Inhibitors
Cell Proliferation
Trametinib
MEK inhibitor
Oncogene
Articles
Cell cycle
medicine.disease
Xenograft Model Antitumor Assays
Pancreatic Neoplasms
030104 developmental biology
medicine.anatomical_structure
Oncology
030220 oncology & carcinogenesis
Mutation
Cancer research
Adenocarcinoma
Female
Carcinoma, Pancreatic Ductal
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 17912423 and 10196439
- Volume :
- 56
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- International Journal of Oncology
- Accession number :
- edsair.doi.dedup.....45ba6cb11a368db441da6b140f6227b0