Establishment of a novel human cell line retaining the characteristics of the original pancreatic adenocarcinoma, and evaluation of MEK as a therapeutic target

0301 basic medicine Cell Survival Pyridones Cell Culture Techniques Articles Pyrimidinones Xenograft Model Antitumor Assays 3. Good health Pancreatic Neoplasms Mice 03 medical and health sciences Mutation Tumor Cells, Cultured Animals Humans Female Protein Kinase Inhibitors Carcinoma, Pancreatic Ductal Cell Proliferation Signal Transduction
DOI: 10.3892/ijo.2020.4965 Publication Date: 2020-01-20T09:14:11Z
ABSTRACT
Pancreatic cancer is a lethal solid malignancy with limited therapeutic options. The development of novel drugs requires adequate new cell line models. A pancreatic line, designated PDXPC1, was established from one ductal adenocarcinoma (PDAC) patient‑derived xenograft. PDXPC1 cells were stably cultured for >2 years and had stable short tandem repeat profile. retained the key mutations primary tumor, along epithelial origin other important protein expression. induced rapid in vivo tumor growth, both subcutaneously orthotopically, mouse model an elevated CA199 level. showed weak invasion migration potency compared to another but relatively resistant multiple anti‑cancer drugs. Interestingly, MEK inhibitor trametinib significantly inhibited proliferation cells, not that Panc‑1 by inactivating MEK/ERK/MYC signaling activating apoptotic pathway via Bcl‑2 degradation. In conclusion, capturing major characteristics may be suitable tool studying underlying mechanisms chemo‑resistance PDAC developing targeted
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